About HOXB13
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
HOXB13 c.567C>T, p.(Asn189=)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
This variant is present at extremely low frequency in population databases. In gnomAD v2.1, the allele frequency is 0.00991% (28/282,626 alleles, 0 homozygotes; grpmax FAF=0.0715%). In gnomAD v4.1, the allele frequency is 0.00452% (73/1,614,196 alleles, 0 homozygotes; grpmax FAF=0.0589%). Both global AF and grpmax FAF are well below the 0.1% threshold for PM2. It is absent from gnomAD-Canada v1.0. The highest sub-population frequency is in the African/African American population (v2.1: 0.10%, v4.1: 0.075%).
Benign criteria applied · 1
BP6Supporting
BP6 · supporting
Multiple reputable clinical diagnostic laboratories have independently classified NM_006361.6:c.567C>T as Benign or Likely benign in ClinVar (VariationID 483492). Specifically: 4 clinical laboratories classify as Likely benign (GeneDx, Ambry Genetics, KCCC/NGS Laboratory, Sinai Health System), 3 as Benign (Labcorp/Women's Health and Genetics, Myriad Genetics), and 1 as benign (Quest Diagnostics). These are established clinical testing laboratories with criteria-provided classifications. The underlying variant-specific evidence used by these laboratories is not publicly available for independent evaluation, satisfying the BP6 requirement.
Recorded classification: Uncertain significance
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BP6 supporting; combination = 1 supporting + 1 supporting benign, which maps to VUS because the evidence is conflicting.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
73 / 1,614,196 alleles
gnomAD v4.1: 73 / 1,614,196 alleles. Recorded AF 4.52238e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 9.90709e-05; MAF= 0.00991%, 28/282626 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.00100152; MAF= 0.10015%, 25/24962 alleles, homozygotes = 0); grpmax FAF= 0.00071547.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
8 reported laboratory submissions
4 Likely benign · 3 Benign · 1 benign.
Functional evidence
Statement recorded
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 17 not met · 1 not assessed · 6 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_006361.6:c.567C>T is a synonymous variant in HOXB13 (p.Asn189=) that does not alter the amino acid sequence.
This variant is extremely rare in population databases, present at an allele frequency of 0.00991% in gnomAD v2.1 (28/282,626 alleles) and 0.00452% in gnomAD v4.1 (73/1,614,196 alleles), with no homozygotes observed, satisfying PM2 at supporting level.
Multiple reputable clinical diagnostic laboratories (8 independent submissions) have classified this variant as Benign or Likely benign in ClinVar (VariationID 483492), with the underlying variant-specific evidence not publicly available for independent evaluation, satisfying BP6 at supporting level.
SpliceAI predicts no splicing impact (max delta score = 0.00), consistent with the synonymous nature of this variant.
No functional studies, cosegregation data, de novo observations, case-control studies, or computational evidence supporting pathogenicity have been identified for this variant.
The variant lies at codon 189, outside the HOXB13 homeodomain (aa 195-254), and does not fall within a known mutational hotspot or functionally critical domain.
Bulk evidence is sparse: one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP6) are met, yielding a net indeterminate ACMG/AMP classification by strict criteria counting. However, the unanimous benign/likely benign consensus from 8 independent clinical laboratories strongly supports a benign interpretation.
No criteria match.
Met · 2
PM2 SupportingThis variant is present at extremely low frequency in population databases. In gnomAD v2.1, the allele frequency is 0.00991% (28/282,626 alleles, 0 homozygotes; grpmax FAF=0.0715%). In gnomAD v4.1, the allele frequency is 0.00452% (73/1,614,196 alleles, 0 homozygotes; grpmax FAF=0.0589%). Both global AF and grpmax FAF are well below the 0.1% threshold for PM2. It is absent from gnomAD-Canada v1.0. The highest sub-population frequency is in the African/African American population (v2.1: 0.10%, v4.1: 0.075%). Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF=0.00991% (28/282
- 626
- 0 hom)
- grpmax FAF=0.0715%
- gnomAD v4.1: AF=0.00452% (73/1
- 614
- 196
- grpmax FAF=0.0589%
- absent from gnomAD-Canada.
Sources
BP6 SupportingMultiple reputable clinical diagnostic laboratories have independently classified NM_006361.6:c.567C>T as Benign or Likely benign in ClinVar (VariationID 483492). Specifically: 4 clinical laboratories classify as Likely benign (GeneDx, Ambry Genetics, KCCC/NGS Laboratory, Sinai Health System), 3 as Benign (Labcorp/Women's Health and Genetics, Myriad Genetics), and 1 as benign (Quest Diagnostics). These are established clinical testing laboratories with criteria-provided classifications. The underlying variant-specific evidence used by these laboratories is not publicly available for independent evaluation, satisfying the BP6 requirement. Details ▾Hide ▴
Evidence considered
- ClinVar VariationID 483492: Likely benign by 4 clinical labs (GeneDx
- Ambry Genetics
- KCCC
- Sinai Health)
- Benign by 3 labs (Labcorp
- Myriad Genetics)
- benign by 1 lab (Quest Diagnostics)
- 8 total submissions
- all benign/likely benign.
Sources
Not met · 17 · evaluated, threshold not reached
PS2 No de novo occurrences of NM_006361.6:c.567C>T have been reported in ClinVar, the published literature, or public databases. PS2 requires confirmed de novo occurrence with maternity and paternity confirmed in a patient with the disease and no family history. Details ▾Hide ▴
Evidence considered
- Exploratory search of ClinVar and literature found no de novo assertions for this variant.
Still missing
- No de novo reports identified in any source.
Sources
PS3 No well-established in vitro or in vivo functional studies have been published demonstrating a damaging effect of c.567C>T on HOXB13 protein function or splicing. SpliceAI predicts no splicing impact (max delta score = 0.00). No VCEP/CSPEC functional dataset exists for HOXB13. Details ▾Hide ▴
Evidence considered
- SpliceAI delta = 0.00 (no predicted splicing impact)
- no functional assay data available in literature.
Still missing
- No published functional studies assessing the impact of this variant on HOXB13 protein function or mRNA splicing.
Sources
PS4 No case-control studies have been identified comparing the prevalence of c.567C>T in affected individuals versus controls for any HOXB13-associated phenotype (e.g., prostate cancer). The variant is rare in population databases (AF ~0.01% in gnomAD v2.1, ~0.005% in v4.1), which does not provide positive evidence for PS4. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.00991% (28/282
- 626 alleles)
- gnomAD v4.1 AF=0.00452% (73/1
- 614
- 196 alleles)
- no case-control studies found.
Still missing
- No case-control studies comparing allele frequency in affected vs unaffected individuals.
Sources
PM1 The variant is located at codon 189 (Asn189), which lies outside the HOXB13 homeodomain (amino acids 195-254). The region surrounding codon 189 is not an established mutational hotspot, and no evidence supports that this codon resides in a well-characterized functional domain without benign variation. Details ▾Hide ▴
Evidence considered
- Codon 189 is outside the homeodomain (aa 195-254)
- no evidence of a mutational hotspot at this position.
Still missing
- No domain-specific functional data or hotspot analysis supporting PM1 at codon 189.
PM6 No reported instances of de novo occurrence of c.567C>T (without confirmation of paternity and maternity) have been identified in ClinVar, the published literature, or public databases. Details ▾Hide ▴
Evidence considered
- Exploratory search found no assumed de novo assertions for this variant.
Still missing
- No reports of de novo occurrence (even unconfirmed) in any source.
Sources
PP1 No published cosegregation data have been identified for c.567C>T with any HOXB13-associated disease phenotype. No family studies or LOVD entries documenting segregation of this variant with disease were found. Details ▾Hide ▴
Evidence considered
- No cosegregation studies or family data identified in literature or public databases.
Still missing
- No cosegregation data available.
PP3 Multiple lines of in silico evidence do not support a deleterious effect. SpliceAI predicts no splicing impact (max delta score = 0.00). REVEL and BayesDel scores are not available for this variant. The HCI prior is not supported for HOXB13. No computational tool predicts a pathogenic effect. Details ▾Hide ▴
Evidence considered
- SpliceAI delta = 0.00 (no splicing impact)
- REVEL and BayesDel not available
- HCI prior not supported for HOXB13.
Still missing
- REVEL and BayesDel scores not available at this genomic position.
Sources
PP4 No patient-specific phenotype or family history data are available to evaluate whether the clinical presentation is highly specific for a disease with a single genetic etiology. PP4 requires detailed phenotypic information that was not provided for this case. Details ▾Hide ▴
Evidence considered
- No patient phenotype or family history data available.
Still missing
- Patient phenotype and family history data not available for evaluation.
PP5 PP5 requires a reputable source to have recently reported the variant as pathogenic with evidence not available for independent evaluation. In ClinVar (VariationID 483492), this variant is reported as Likely benign by 4 clinical laboratories, Benign by 3 clinical laboratories, and benign by 1 clinical laboratory. No reputable source has reported this variant as pathogenic. Details ▾Hide ▴
Evidence considered
- ClinVar: Likely benign (4 labs)
- Benign (3 labs)
- benign (1 lab)
- no pathogenic assertions from any reputable source.
Sources
BA1 The maximum allele frequency observed in any population is 0.10% (African/African American, gnomAD v2.1), which is well below the 1% threshold for BA1. The grpmax FAF is 0.0715% (v2.1) and 0.0589% (v4.1), both far below 1%. Details ▾Hide ▴
Evidence considered
- Maximum sub-population AF = 0.10% (gnomAD v2.1 African/African American)
- grpmax FAF = 0.0715% v2.1
- 0.0589% v4.1
- all well below 1% threshold.
Sources
BS1 The maximum allele frequency observed is 0.10% (African/African American, gnomAD v2.1), which is below the 0.3% threshold for BS1 under non-VCEP generic ACMG rules. The grpmax FAF is 0.0715% (v2.1) and 0.0589% (v4.1), both below 0.3%. While present in population databases, the frequency does not exceed the expected threshold for a disorder-associated variant. Details ▾Hide ▴
Evidence considered
- Maximum sub-population AF = 0.10% (v2.1)
- 0.075% (v4.1)
- grpmax FAF = 0.0715% v2.1
- 0.0589% v4.1
- all below 0.3% threshold.
Sources
BS2 No specific observations of this variant in healthy adult individuals for a disorder with full penetrance expected at an early age have been identified. While the variant is observed in gnomAD (a population database largely composed of individuals not ascertained for severe pediatric disease), the lack of detailed phenotype data for carriers precludes meeting BS2. Details ▾Hide ▴
Evidence considered
- Variant observed in gnomAD population databases (28-73 alleles)
- but no specific healthy adult carrier phenotype data available for BS2 determination.
Still missing
- No detailed phenotype data available for gnomAD carriers to confirm healthy adult status for a fully penetrant early-onset disorder.
Sources
BS3 No well-established in vitro or in vivo functional studies have been published demonstrating that c.567C>T has no damaging effect on HOXB13 protein function or mRNA splicing. While SpliceAI predicts no splicing impact (max delta = 0.00), this is in silico prediction, not experimental functional evidence. The absence of this variant from COSMIC (somatic cancer database) and OncoKB (Unknown Oncogenic Effect) does not constitute functional evidence. Details ▾Hide ▴
Evidence considered
- SpliceAI delta = 0.00 (in silico only
- not functional assay)
- no published functional studies found
- COSMIC and OncoKB do not provide benign functional evidence.
Still missing
- No experimental functional studies (e.g.
- minigene splicing assay
- protein function assay) demonstrating no effect of this variant.
Sources
BS4 No published family segregation analyses demonstrating lack of segregation of c.567C>T with an HOXB13-associated phenotype have been identified. BS4 requires specific evidence of non-segregation in affected families. Details ▾Hide ▴
Evidence considered
- No family segregation studies found in literature or public databases.
Still missing
- No family segregation data available demonstrating non-segregation with disease.
BP2 No reported observations of c.567C>T in trans with a known pathogenic HOXB13 variant (for a dominant disorder) or in cis with a pathogenic variant in any inheritance pattern. No co-occurrence data with established pathogenic HOXB13 variants were identified in ClinVar, literature, or public databases. Details ▾Hide ▴
Evidence considered
- No reported co-occurrence in trans or cis with pathogenic HOXB13 variants in ClinVar or literature.
Still missing
- No co-occurrence data with known pathogenic HOXB13 variants available.
Sources
BP4 BP4 requires multiple lines of computational evidence suggesting no impact on the gene or gene product. While SpliceAI predicts no splicing impact (max delta = 0.00) for this synonymous variant, this represents only a single line of computational evidence. Conservation data (GERP, phyloP, PhastCons), REVEL, and BayesDel are not available to provide additional computational support. A single line of in silico evidence is insufficient to meet the 'multiple lines' requirement of BP4. Details ▾Hide ▴
Evidence considered
- SpliceAI delta = 0.00 (no predicted splicing impact)
- no additional computational evidence lines available (no REVEL
- BayesDel
- or conservation scores).
Still missing
- No conservation data (GERP
- phyloP
- PhastCons) or additional in silico scores available to satisfy 'multiple lines' requirement.
Sources
BP7 BP7 requires both (1) splicing prediction algorithms predict no impact to the splice consensus sequence nor creation of a new splice site, AND (2) the nucleotide is not highly conserved. The first condition is satisfied: SpliceAI predicts no splicing impact (max delta = 0.00). However, the second condition cannot be evaluated because no nucleotide-level conservation data (GERP, phyloP, PhastCons) are available for this genomic position. Without conservation evidence, BP7 cannot be fully met. Details ▾Hide ▴
Evidence considered
- SpliceAI delta = 0.00 (no splicing impact
- satisfies condition 1)
- no conservation data available to evaluate condition 2.
Still missing
- No nucleotide conservation scores (GERP
- phyloP
- PhastCons) available at this genomic position.
Sources
Not assessed · 1 · no assessment recorded
BP5 BP5 requires the variant to be found in a case with an alternate molecular basis for disease. No case-specific clinical or molecular data were provided for the individual in whom this variant was identified, and no alternate molecular diagnosis has been documented. Details ▾Hide ▴
Evidence considered
- No case-level clinical or molecular data available.
Still missing
- No case data available to evaluate whether an alternate molecular basis for disease exists.
Not applicable · 6· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_006361.6:c.567C>T is a synonymous variant (p.Asn189=) that does not introduce a premature termination codon, disrupt an initiator codon, or alter a canonical splice site. Per ClinGen SVI PVS1 recommendations (PMC6185798), this variant does not fall into any null-variant bucket, and the automated PVS1 assessment confirms it is not eligible for generic PVS1 framework application. Details ▾Hide ▴
Evidence considered
- Synonymous variant (p.Asn189=)
- no null-variant mechanism applicable.
Sources
PS1 N/APS1 applies when the same amino acid change has been established as pathogenic via a different nucleotide change. This variant is synonymous (p.Asn189=) and does not alter the amino acid sequence; there is no pathogenic amino acid change at this position to compare against. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- no pathogenic amino acid change at this position exists.
PM5 N/APM5 requires a novel missense change at the same amino acid residue as a known pathogenic missense variant. This variant is synonymous (p.Asn189=) and does not alter the amino acid. The automated PM5 candidate harvesting confirmed no eligible same-residue comparators. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- no same-residue missense comparators identified. pm5_candidates.json confirms not eligible.
Sources
pm5_candidates
PP2 N/APP2 applies specifically to missense variants in genes with a low rate of benign missense variation where missense variants are a common mechanism of disease. This variant is synonymous (p.Asn189=), not missense. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- PP2 is a missense-specific criterion.
BP1 N/ABP1 applies specifically to missense variants in genes where primarily truncating variants are known to cause disease. This variant is synonymous (p.Asn189=), not missense. Additionally, HOXB13-associated disease (prostate cancer risk) involves both missense (e.g., G84E) and other variant types. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- BP1 is specific to missense variants in genes with primarily truncating disease mechanisms.
PS5 N/APS5 applies when a novel missense change occurs at an amino acid residue where a different missense change has been established as pathogenic. This variant is synonymous (p.Asn189=) and does not alter the amino acid; it represents a less severe molecular consequence than any potential missense change at this position. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- PS5 requires a more severe molecular consequence than an established pathogenic missense change.
Identifiers
- Gene
- HOXB13
- Transcript
- NM_006361.6
- Coding (HGVS c.)
- NM_006361.6:c.567C>T
- Protein (HGVS p.)
- NP_006352.2:p.(Asn189=)
- GRCh38
- chr17:48728027 G>A
- GRCh37
- chr17:46805389 G>A
- ClinVar
- 483492
Gene diagram
Every interpreted variant in HOXB13, mapped onto the exon structure of NM_006361.6. Select a row to find it on the plot.
HOXB13NM_006361.6
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in HOXB13
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
73 / 1,614,196 alleles
AF 4.52e-05 · 0 homozygotes · FAF 0.000589
gnomAD v2.1
28 / 282,626 alleles
AF 9.91e-05 · 0 homozygotes · FAF 0.000715
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 4.5e-05 · 73 / 1,614,196 alleles · 0 hom · FAF 0.00059
| African/African American56 / 75,056 | 0.00075 |
| Middle Eastern1 / 6,062 | 0.00016 |
| Admixed American8 / 60,030 | 0.00013 |
| Remaining individuals7 / 62,510 | 0.00011 |
| European (Finnish)1 / 64,028 | 1.6e-05 |
0 alternate alleles recorded in 5 other groups: Amish, East Asian, South Asian, Ashkenazi Jewish, European (non-Finnish).
gnomAD v2.1
AF 9.9e-05 · 28 / 282,626 alleles · 0 hom · FAF 0.00072
| African/African American25 / 24,962 | 0.001 |
| Admixed American3 / 35,432 | 8.5e-05 |
0 alternate alleles recorded in 6 other groups: Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 4.52238e-05; MAF= 0.00452%, 73/1614196 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.00074611; MAF= 0.07461%, 56/75056 alleles, homozygotes = 0); grpmax FAF= 0.00058932.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 9.90709e-05; MAF= 0.00991%, 28/282626 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.00100152; MAF= 0.10015%, 25/24962 alleles, homozygotes = 0); grpmax FAF= 0.00071547.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 Multiple lines of in silico evidence do not support a deleterious effect. SpliceAI predicts no splicing impact (max delta score = 0.00). REVEL and BayesDel scores are not available for this variant. The HCI prior is not supported for HOXB13. No computational tool predicts a pathogenic effect. Details ▾Hide ▴
Evidence considered
- SpliceAI delta = 0.00 (no splicing impact)
- REVEL and BayesDel not available
- HCI prior not supported for HOXB13.
Still missing
- REVEL and BayesDel scores not available at this genomic position.
Sources
BP4 BP4 requires multiple lines of computational evidence suggesting no impact on the gene or gene product. While SpliceAI predicts no splicing impact (max delta = 0.00) for this synonymous variant, this represents only a single line of computational evidence. Conservation data (GERP, phyloP, PhastCons), REVEL, and BayesDel are not available to provide additional computational support. A single line of in silico evidence is insufficient to meet the 'multiple lines' requirement of BP4. Details ▾Hide ▴
Evidence considered
- SpliceAI delta = 0.00 (no predicted splicing impact)
- no additional computational evidence lines available (no REVEL
- BayesDel
- or conservation scores).
Still missing
- No conservation data (GERP
- phyloP
- PhastCons) or additional in silico scores available to satisfy 'multiple lines' requirement.
Sources
BP7 BP7 requires both (1) splicing prediction algorithms predict no impact to the splice consensus sequence nor creation of a new splice site, AND (2) the nucleotide is not highly conserved. The first condition is satisfied: SpliceAI predicts no splicing impact (max delta = 0.00). However, the second condition cannot be evaluated because no nucleotide-level conservation data (GERP, phyloP, PhastCons) are available for this genomic position. Without conservation evidence, BP7 cannot be fully met. Details ▾Hide ▴
Evidence considered
- SpliceAI delta = 0.00 (no splicing impact
- satisfies condition 1)
- no conservation data available to evaluate condition 2.
Still missing
- No nucleotide conservation scores (GERP
- phyloP
- PhastCons) available at this genomic position.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
4 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
-
PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Richards S et al. · 2015No paper-specific finding is recorded.
-
PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.Karbassi I et al. · 2016No paper-specific finding is recorded.
-
PMID 25394175 ↗A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.Hampel H et al. · 2015No paper-specific finding is recorded.
-
PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Nykamp K et al. · 2017No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
73 / 1,614,196 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
4 Likely benign · 3 Benign · 1 benign
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/483492/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-46805389-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-48728027-G-A?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_006361.6%3Ac.567C…
- OncoKB ↗www.oncokb.org/gene/HOXB13/N189=
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=HOXB13+c.567C%3ET
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 4.52238e-05; MAF= 0.00452%, 73/1614196 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.00074611; MAF= 0.07461%, 56/75056 alleles, homozygotes = 0); grpmax FAF= 0.00058932.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 9.90709e-05; MAF= 0.00991%, 28/282626 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.00100152; MAF= 0.10015%, 25/24962 alleles, homozygotes = 0); grpmax FAF= 0.00071547.
ClinVar
This variant has been reported in ClinVar as Likely benign (4 clinical laboratories) and as Benign (3 clinical laboratories) and as benign (1 clinical laboratory). (ClinVarID = 483492)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Functional
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.