About TP53
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
TP53 c.390C>T, p.(Leu130=)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign classification under the recorded framework.
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 ClinGen TP53 VCEP v2.4. 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: 0
Benign evidence criteria: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BP4Supporting
BP4 · supporting
NM_000546.6:c.390C>T is a silent/synonymous variant outside the canonical splice sites (±1,2 positions). SpliceAI predicts no splicing impact (max delta score = 0.01, ≤0.1 threshold for silent variants). Per the TP53 VCEP BP4 rules for silent/intronic variants: SpliceAI ≤0.1 satisfies BP4_Supporting. Note: BP7 is the more specific code for synonymous variants and is assessed separately; BP4 is reported here per the VCEP specification which lists BP4 as a prerequisite for BP7_Supporting.
BP7Supporting
BP7 · supporting
NM_000546.6:c.390C>T is a synonymous variant at position c.390 within exon 5 (c.376-c.559). The variant is outside the core splice motif (last three nucleotides and first nucleotide of the exon). SpliceAI predicts no impact to the splice consensus and no creation of a new splice site (max delta score = 0.01 ≤ 0.1, BP4 criterion met). Per the TP53 VCEP BP7_Supporting rule for synonymous variants outside the core splice motif with SpliceAI ≤0.1, this criterion is met at supporting benign strength.
Recorded classification: Likely benign
ClinGen TP53 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TP53 Version 2.4 v2.4 point-based framework: BP4 supporting benign (-1) + BP7 supporting benign (-1) = -2 points, which maps to Likely Benign.
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
12 / 1,613,912 alleles
gnomAD v4.1: 12 / 1,613,912 alleles. Recorded AF 7.43535e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 2.39663e-05; MAF= 0.00240%, 6/250352 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 5.78637e-05; MAF= 0.00579%, 2/34564 alleles, homozygotes = 0); grpmax FAF= 9.58e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
No listed criterion applied
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
9 reported laboratory submissions
7 Likely benign · 1 Likely Benign · 1 Benign. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
Context only
ClinVar ↗
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
4 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV52782624, n = 4 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen TP53 VCEP v2.4, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 7 not met · 7 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000546.6:c.390C>T (p.Leu130=) is a synonymous variant in exon 5 of TP53. SpliceAI predicts no splicing impact (max delta score 0.01). The variant is present at very low frequency in gnomAD (v2.1: 6/250,352 alleles; v4.1: 12/1,613,912 alleles) though the Admixed American subpopulation carries multiple alleles with AF above the PM2 subpopulation ceiling. BP7_Supporting is met as a synonymous variant outside the core splice motif with no predicted splicing effect.
No pathogenic criteria are met. PVS1, PS1, and PM5 are not applicable (synonymous variant). PM1 is not met (not a missense at a VCEP-designated hotspot codon). PM2 is not met (AMR subpopulation AF exceeds 0.004% ceiling). PS3 and BS3 are not met (VCEP functional rules apply only to missense and in-frame deletions). No proband-level clinical data were available to assess PS2, PS4, PP1, PP4, BS2, or BS4.
The only met criterion is BP7_Supporting (-1 point under the Tavtigian Bayesian point system). This places the variant in the VUS range (total points = -1). No pathogenic evidence criteria are met to elevate classification.
No criteria match.
Met · 2
BP4 SupportingNM_000546.6:c.390C>T is a silent/synonymous variant outside the canonical splice sites (±1,2 positions). SpliceAI predicts no splicing impact (max delta score = 0.01, ≤0.1 threshold for silent variants). Per the TP53 VCEP BP4 rules for silent/intronic variants: SpliceAI ≤0.1 satisfies BP4_Supporting. Note: BP7 is the more specific code for synonymous variants and is assessed separately; BP4 is reported here per the VCEP specification which lists BP4 as a prerequisite for BP7_Supporting. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.01 (≤0.1)
- Synonymous variant outside core splice motif
- VCEP BP4_Supporting rule for silent/intronic variants
Sources
BP7 SupportingNM_000546.6:c.390C>T is a synonymous variant at position c.390 within exon 5 (c.376-c.559). The variant is outside the core splice motif (last three nucleotides and first nucleotide of the exon). SpliceAI predicts no impact to the splice consensus and no creation of a new splice site (max delta score = 0.01 ≤ 0.1, BP4 criterion met). Per the TP53 VCEP BP7_Supporting rule for synonymous variants outside the core splice motif with SpliceAI ≤0.1, this criterion is met at supporting benign strength. Details ▾Hide ▴
Evidence considered
- Synonymous variant c.390C>T (p.Leu130=) at codon 130 in exon 5
- Outside core splice motif (exon 5 boundaries: c.376-c.559)
- SpliceAI max delta = 0.01 (≤0.1
- BP4 met)
- VCEP BP7_Supporting rule satisfied
Sources
Not met · 7 · evaluated, threshold not reached
PS3 The TP53 VCEP functional assay rules (PS3/BS3 flowchart and Functional-worksheet.xlsx) apply only to missense amino acid substitutions and small in-frame deletions. NM_000546.6:c.390C>T is a synonymous variant with no predicted amino acid change; the VCEP functional framework does not provide for assessment of synonymous variants. No variant-specific functional data were identified in the literature. Details ▾Hide ▴
Evidence considered
- VCEP PS3/BS3 rules restrict functional evidence codes to missense and in-frame deletion variants
- synonymous variants are out of scope
Sources
PM1 The TP53 VCEP restricts PM1 to missense variants at specified hotspot codons (175, 245, 248, 249, 273, 282) or germline missense variants with sufficient somatic occurrences at cancerhotspots.org. NM_000546.6:c.390C>T is a synonymous variant at codon 130, which is not among the VCEP-defined PM1 hotspot codons and is not a missense variant. Details ▾Hide ▴
Evidence considered
- VCEP PM1 rules: hotspot codons are 175
- 245
- 248
- 249
- 273
- 282 (missense only)
- codon 130 not eligible
Sources
PM2 Total gnomAD allele frequencies are below the VCEP PM2_Supporting threshold of 0.003% (v2.1: AF=0.00240%, 6/250352; v4.1: AF=0.00074%, 12/1613912). However, the Admixed American (AMR) subpopulation carries multiple alleles with an AF exceeding the 0.004% subpopulation ceiling in both gnomAD versions (v2.1: 2/34564, AF=0.00579%; v4.1: 5/59998, AF=0.00833%). Under the TP53 VCEP rule, when multiple alleles are present in any non-founder genetic ancestry group, that group's AF must remain below 0.004%. This criterion is not met. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: total AF=0.00240%
- AMR=2 alleles
- AF=0.00579% (>0.004%)
- gnomAD v4.1: total AF=0.00074%
- AMR=5 alleles
- AF=0.00833% (>0.004%)
Sources
PP3 The TP53 VCEP PP3 rules for missense variants require aGVGD class C25-C65 or C65 with BayesDel ≥0.16; for exonic variants with predicted splicing effect, SpliceAI ≥0.2 is required. NM_000546.6:c.390C>T is a synonymous variant with SpliceAI max delta of 0.01, well below the 0.2 threshold. No evidence supports a pathogenic computational prediction for this variant. The variant is absent from the VCEP PP3-BP4-codes.xlsx pre-computed assignments. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.01 (<0.2 threshold for PP3)
- Not listed in VCEP PP3-BP4-codes.xlsx
Sources
BA1 The TP53 VCEP BA1 threshold is a filtering allele frequency (FAF) ≥0.001 (0.1%) in a non-founder gnomAD continental subpopulation. The grpmax FAF for this variant is 3.233e-05 (v4.1) and 9.58e-06 (v2.1), both far below the 0.001 threshold. Details ▾Hide ▴
Evidence considered
- grpmax FAF v2.1: 9.58e-06
- grpmax FAF v4.1: 3.233e-05
- Both well below BA1 threshold of 0.001
Sources
BS1 The TP53 VCEP BS1 threshold is a filtering allele frequency (FAF) ≥0.0003 but <0.001 in a non-founder gnomAD continental subpopulation with ≥2000 alleles and ≥2 alleles present. The grpmax FAF is 3.233e-05 (v4.1), below the 0.0003 minimum threshold. Details ▾Hide ▴
Evidence considered
- grpmax FAF v4.1: 3.233e-05
- Below BS1 minimum threshold of 0.0003
Sources
BS3 The TP53 VCEP functional assay rules (BS3 flowchart and Functional-worksheet.xlsx) apply only to missense amino acid substitutions and small in-frame deletions. NM_000546.6:c.390C>T is a synonymous variant with no predicted amino acid change; the VCEP functional framework does not provide for assessment of synonymous variants. No functional evidence demonstrating normal protein function was identified for this specific variant. Details ▾Hide ▴
Evidence considered
- VCEP BS3 rules restricted to missense and in-frame deletions
- synonymous out of scope
Sources
Not assessed · 7 · no assessment recorded
PS2 No de novo observation data were provided for this case. PS2 requires proband-level data with cancer history and confirmed parentage for scoring under the TP53 VCEP LFS points system. Details ▾Hide ▴
Still missing
- No proband data provided
- unable to assess de novo status
PS4 No proband-level case data with LFS cancer diagnoses were provided. PS4 under the TP53 VCEP requires proband counts scored against the LFS cancer points table (PS4-Points-Table.pdf) to determine strength. Details ▾Hide ▴
Still missing
- No proband cancer phenotype data provided
- unable to calculate PS4 points
PP1 No cosegregation data were provided. PP1 under the TP53 VCEP requires meiotic counts across families (3-4 meioses for supporting, 5-6 for moderate, ≥7 for strong). Details ▾Hide ▴
Still missing
- No family segregation data provided
PP4 No variant allele fraction (VAF) data were provided. PP4 under the TP53 VCEP requires VAF observations in the 5-35% range to assess clonal hematopoiesis/mosaicism patterns. Details ▾Hide ▴
Still missing
- No VAF data provided
BS2 No data on unrelated females aged ≥60 years without cancer were provided. BS2 under the TP53 VCEP requires counts of unaffected elderly females from a single source. Details ▾Hide ▴
Still missing
- No healthy elderly female data provided
BS4 No segregation data in affected family members were provided. BS4 under the TP53 VCEP requires demonstration of lack of segregation in family members with LFS-associated cancers. Details ▾Hide ▴
Still missing
- No family segregation data provided
PS5 PS5 is not part of the standard ACMG/AMP criteria set for this assessment task. Details ▾Hide ▴
No further detail was recorded.
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 applies only to null variants (nonsense, frameshift, canonical splice sites, initiation codon, exon deletions). NM_000546.6:c.390C>T is a synonymous variant (NP_000537.3:p.Leu130=) and does not fall into any PVS1-eligible variant class per the TP53 VCEP PVS1 flowchart. Details ▾Hide ▴
No further detail was recorded.
PS1 N/APS1 applies when the variant produces the same amino acid change as a previously established pathogenic variant. NM_000546.6:c.390C>T is synonymous (p.Leu130=) and produces no amino acid change, so there is no comparator amino acid change to evaluate. Details ▾Hide ▴
No further detail was recorded.
PM5 N/APM5 applies to missense variants at an amino acid residue where a different pathogenic/likely pathogenic missense change has been reported. NM_000546.6:c.390C>T is a synonymous variant (p.Leu130=); PM5 is not applicable to synonymous variants. Details ▾Hide ▴
No further detail was recorded.
PM6 VCEPThe TP53 VCEP merges PM6 with PS2 into a single combined de novo rule; PM6 is listed as Not Applicable in the VCEP specification. Details ▾Hide ▴
PP2 VCEPThe TP53 VCEP lists PP2 as Not Applicable. Details ▾Hide ▴
PP5 VCEPThe TP53 VCEP explicitly marks PP5 as Not Applicable for this VCEP, per ClinGen Sequence Variant Interpretation VCEP Review Committee recommendation. Details ▾Hide ▴
BP1 VCEPThe TP53 VCEP lists BP1 as Not Applicable; truncating variants account for only a portion of disease-causing variants in TP53. Details ▾Hide ▴
BP2 VCEPThe TP53 VCEP lists BP2 as Not Applicable. Details ▾Hide ▴
BP5 VCEPThe TP53 VCEP lists BP5 as Not Applicable. Details ▾Hide ▴
BP6 VCEPThe TP53 VCEP explicitly marks BP6 as Not Applicable for this VCEP, per ClinGen Sequence Variant Interpretation VCEP Review Committee recommendation. Details ▾Hide ▴
Identifiers
- Gene
- TP53
- Transcript
- NM_000546.6
- Coding (HGVS c.)
- NM_000546.6:c.390C>T
- Protein (HGVS p.)
- NP_000537.3:p.(Leu130=)
- GRCh38
- chr17:7675222 G>A
- GRCh37
- chr17:7578540 G>A
- ClinVar
- 233110, 186498
- COSMIC
- COSV52782624
Gene diagram
Every interpreted variant in TP53, mapped onto the exon structure of NM_000546.6. Select a row to find it on the plot.
TP53NM_000546.6
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 TP53
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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
12 / 1,613,912 alleles
AF 7.44e-06 · 0 homozygotes · FAF 3.23e-05
gnomAD v2.1
6 / 250,352 alleles
AF 2.4e-05 · 0 homozygotes · FAF 9.58e-06
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 7.4e-06 · 12 / 1,613,912 alleles · 0 hom · FAF 3.2e-05
| Admixed American5 / 59,998 | 8.3e-05 |
| South Asian1 / 91,090 | 1.1e-05 |
| European (non-Finnish)6 / 1,179,950 | 5.1e-06 |
0 alternate alleles recorded in 7 other groups: Remaining individuals, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 2.4e-05 · 6 / 250,352 alleles · 0 hom · FAF 9.6e-06
| Admixed American2 / 34,564 | 5.8e-05 |
| East Asian1 / 18,392 | 5.4e-05 |
| European (non-Finnish)3 / 112,774 | 2.7e-05 |
0 alternate alleles recorded in 5 other groups: African/African American, Ashkenazi Jewish, European (Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 7.43535e-06; MAF= 0.00074%, 12/1613912 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 8.33361e-05; MAF= 0.00833%, 5/59998 alleles, homozygotes = 0); grpmax FAF= 3.233e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 2.39663e-05; MAF= 0.00240%, 6/250352 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 5.78637e-05; MAF= 0.00579%, 2/34564 alleles, homozygotes = 0); grpmax FAF= 9.58e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingNM_000546.6:c.390C>T is a silent/synonymous variant outside the canonical splice sites (±1,2 positions). SpliceAI predicts no splicing impact (max delta score = 0.01, ≤0.1 threshold for silent variants). Per the TP53 VCEP BP4 rules for silent/intronic variants: SpliceAI ≤0.1 satisfies BP4_Supporting. Note: BP7 is the more specific code for synonymous variants and is assessed separately; BP4 is reported here per the VCEP specification which lists BP4 as a prerequisite for BP7_Supporting. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.01 (≤0.1)
- Synonymous variant outside core splice motif
- VCEP BP4_Supporting rule for silent/intronic variants
Sources
BP7 SupportingNM_000546.6:c.390C>T is a synonymous variant at position c.390 within exon 5 (c.376-c.559). The variant is outside the core splice motif (last three nucleotides and first nucleotide of the exon). SpliceAI predicts no impact to the splice consensus and no creation of a new splice site (max delta score = 0.01 ≤ 0.1, BP4 criterion met). Per the TP53 VCEP BP7_Supporting rule for synonymous variants outside the core splice motif with SpliceAI ≤0.1, this criterion is met at supporting benign strength. Details ▾Hide ▴
Evidence considered
- Synonymous variant c.390C>T (p.Leu130=) at codon 130 in exon 5
- Outside core splice motif (exon 5 boundaries: c.376-c.559)
- SpliceAI max delta = 0.01 (≤0.1
- BP4 met)
- VCEP BP7_Supporting rule satisfied
Sources
PP3 The TP53 VCEP PP3 rules for missense variants require aGVGD class C25-C65 or C65 with BayesDel ≥0.16; for exonic variants with predicted splicing effect, SpliceAI ≥0.2 is required. NM_000546.6:c.390C>T is a synonymous variant with SpliceAI max delta of 0.01, well below the 0.2 threshold. No evidence supports a pathogenic computational prediction for this variant. The variant is absent from the VCEP PP3-BP4-codes.xlsx pre-computed assignments. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.01 (<0.2 threshold for PP3)
- Not listed in VCEP PP3-BP4-codes.xlsx
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
7 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
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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.Standards and guidelines for the interpretation of sequence variants (ACMG/AMP 2015). A consensus recommendation document describing the general ACMG/AMP variant classification framework. Does not discuss any specific TP53 variant.Does not name this variant
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PMID 15604628 ↗Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.Trepanier A et al. · 2004Genetic cancer risk assessment and counseling recommendations of the National Society of Genetic Counselors. Describes the process of cancer genetic counseling and risk assessment for hereditary cancer syndromes. Lists Li-Fraumeni syndrome as a rare hereditary cancer syndrome but does not discuss specific TP53 variants.Does not name this variant
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PMID 20301488 ↗Li-Fraumeni Syndrome.Adam MP et al. · 1993Li-Fraumeni Syndrome GeneReviews entry. Summarizes clinical characteristics, diagnosis, and management of LFS. A general review of TP53-related disease; does not discuss NM_000546.6:c.390C>T.Does not name this variant
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PMID 23788249 ↗ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.Green RC et al. · 2013ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Provides guidance on which genes should be reported as secondary findings. Does not discuss any specific TP53 variant.Does not name this variant
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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. · 2015ACMG/NSGC practice guideline on referral indications for cancer predisposition assessment. Provides referral criteria for hereditary cancer syndromes based on personal and family cancer history. Does not discuss any specific TP53 variant.Does not name this variant
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PMID 26140447 ↗Points to Consider: Ethical, Legal, and Psychosocial Implications of Genetic Testing in Children and Adolescents.Points to consider regarding ethical, legal, and psychosocial implications of genetic testing in children and adolescents. A policy statement without discussion of specific variants.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Describes an alternative classification framework; does not provide evidence for any specific variant.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
12 / 1,613,912 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.010
Open source ↗
ClinVar
7 Likely benign · 1 Likely 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 ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/135637581
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/186498/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-7578540-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-7675222-G-A?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/17-7675222-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000546.6%3Ac.390C…
- OncoKB ↗www.oncokb.org/gene/TP53/L130=
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=121517784
- 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= 7.43535e-06; MAF= 0.00074%, 12/1613912 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 8.33361e-05; MAF= 0.00833%, 5/59998 alleles, homozygotes = 0); grpmax FAF= 3.233e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 2.39663e-05; MAF= 0.00240%, 6/250352 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 5.78637e-05; MAF= 0.00579%, 2/34564 alleles, homozygotes = 0); grpmax FAF= 9.58e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Likely benign (7 clinical laboratories) and as Likely Benign (1 clinical laboratory) and as Benign (1 clinical laboratory). (ClinVarID = 186498)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
Functional
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
Somatic
This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV52782624, n = 4 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.