About APC
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
APC c.1636C>T, p.(Arg546Ter)
Classification
Likely pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely pathogenic. Select a step to read what it means.
Likely pathogenic.A likely pathogenic 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 APC VCEP v2.1.0. 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: 2
Benign evidence criteria: 0
Pathogenic criteria applied · 2
PVS1Very strong
PVS1 · very strong
NM_001127511.3:c.1636C>T is a nonsense variant (p.Arg546Ter) in APC, a gene where loss of function is the established disease mechanism for familial adenomatous polyposis. The premature termination codon at position 546 lies upstream of the last exon-exon junction (c.1904/1905) by 269 nucleotides, well beyond the 50-55 nucleotide NMD boundary, predicting nonsense-mediated decay. Under the ClinGen InSiGHT APC VCEP v2.1.0, null variants in APC qualify for PVS1.
PM2Supporting
PM2 · supporting
NM_001127511.3:c.1636C>T is absent from gnomAD v2.1 and present at extremely low frequency in gnomAD v4.1 (1/1,613,730 alleles; AF=6.2e-7). Under the APC VCEP v2.1.0, PM2_Supporting is met when the allele count is ≤1 and the allele frequency is <0.001% (0.00001). The observed AF of 0.000062% is below this threshold.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Likely pathogenic
ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for APC Version 2.1.0 v2.1.0 criteria-combination framework: matched Rule20 (1 Pathogenic.Very Strong + 1 Pathogenic.Supporting) with applied criteria: PVS1 very strong, PM2 supporting; maps to Likely Pathogenic.
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
1 / 1,613,730 alleles
gnomAD v4.1: 1 / 1,613,730 alleles. Recorded AF 6.19682e-07. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
17 reported laboratory submissions
16 Pathogenic · 1 Uncertain significance.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
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 ClinGen APC VCEP v2.1.0, with the data and sources behind each one.
27 criteria with recorded statuses: 2 met · 4 not met · 10 not assessed · 11 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_001127511.3:c.1636C>T (p.Arg546Ter) is a nonsense variant in APC, a gene where loss of function is the established mechanism for familial adenomatous polyposis.
This variant introduces a premature termination codon at position 546, upstream of the last exon-exon junction, predicting nonsense-mediated decay and complete loss of the C-terminal 2297 amino acids including all β-catenin binding and regulatory domains.
The variant is absent from gnomAD v2.1 and present at extremely low frequency in gnomAD v4.1 (1/1,613,730 alleles; AF=6.2×10⁻⁷), meeting PM2_Supporting under APC VCEP v2.1.0.
ClinVar classifies this variant as Pathogenic based on submissions from multiple clinical laboratories, though individual case-level phenotype annotation is not publicly available for PS4 assessment.
SpliceAI predicts no cryptic splice impact (max delta=0.01), consistent with this being a straightforward null variant rather than a splicing defect.
No criteria match.
Met · 2
PVS1 Very strongNM_001127511.3:c.1636C>T is a nonsense variant (p.Arg546Ter) in APC, a gene where loss of function is the established disease mechanism for familial adenomatous polyposis. The premature termination codon at position 546 lies upstream of the last exon-exon junction (c.1904/1905) by 269 nucleotides, well beyond the 50-55 nucleotide NMD boundary, predicting nonsense-mediated decay. Under the ClinGen InSiGHT APC VCEP v2.1.0, null variants in APC qualify for PVS1. Details ▾Hide ▴
Evidence considered
- Nonsense variant p.Arg546Ter creates a premature termination codon in exon 12 of 14
- APC is a gene where LOF is the predominant disease mechanism per APC VCEP v2.1.0
- Variant is upstream of the last exon-exon junction with NMD predicted (PMC6185798)
- Absent from gnomAD v2.1
- single allele in gnomAD v4.1 (AF=6.2e-7)
Still missing
- No direct experimental evidence of NMD or absence of full-length APC protein for this specific variant
Sources
PM2 SupportingNM_001127511.3:c.1636C>T is absent from gnomAD v2.1 and present at extremely low frequency in gnomAD v4.1 (1/1,613,730 alleles; AF=6.2e-7). Under the APC VCEP v2.1.0, PM2_Supporting is met when the allele count is ≤1 and the allele frequency is <0.001% (0.00001). The observed AF of 0.000062% is below this threshold. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1
- gnomAD v4.1: AC=1
- AF=6.2e-7 (0.000062%)
- max subpopulation AF=8.48e-7 in NFE
- Below APC VCEP PM2_Supporting threshold of <0.001% with AC≤1
Sources
Not met · 4 · evaluated, threshold not reached
PS1 PS1 requires the same amino acid change as a previously established pathogenic variant. NM_001127511.3:c.1636C>T creates a premature stop codon (p.Arg546Ter), a nonsense change. There is no previously classified pathogenic nonsense variant at codon 546 identified in ClinVar or the APC VCEP records to satisfy PS1. The APC VCEP specifies PS1 applies only to missense and splice variants. Details ▾Hide ▴
Evidence considered
- This is a nonsense variant
- not a missense or splice variant
- APC VCEP PS1 rule applies only to missense and splice variants
Sources
cspec ↗pm5_candidates
PP3 Under the APC VCEP v2.1.0, PP3 is applicable only to missense variants (via in silico splicing predictors to reveal possible splice effects) and non-canonical splicing variants. NM_001127511.3:c.1636C>T is a nonsense variant. SpliceAI predicts no significant splice impact (max delta score = 0.01). BayesDel score of 0.66 is not actionable under the VCEP PP3 rule, which prohibits use of conservation/evolutionary prediction models for missense variants and is silent on nonsense variants. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.01: no predicted splice impact
- BayesDel = 0.66
- but VCEP PP3 rule excludes conservation-based predictions
- PP3 is intended for missense and non-canonical splicing variants
- not nonsense variants
Sources
BA1 Under the APC VCEP v2.1.0, BA1 requires a gnomAD Popmax Filtering AF ≥0.1% (0.001). NM_001127511.3:c.1636C>T has a maximum population AF of 8.48e-7 (0.00008%) in European non-Finnish, far below the BA1 threshold. The variant is effectively absent from population databases. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: absent
- gnomAD v4.1 max population AF = 8.48e-7 (NFE)
- well below BA1 threshold of ≥0.1%
Sources
BS1 Under the APC VCEP v2.1.0, BS1 requires a gnomAD Popmax Filtering AF ≥0.001% (0.00001). NM_001127511.3:c.1636C>T has a maximum population AF of 8.48e-7 (0.00008%) in European non-Finnish, which is below the BS1 threshold of 0.001%. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 max population AF = 8.48e-7
- below BS1 threshold of ≥0.001%
Sources
Not assessed · 10 · no assessment recorded
PS2 No de novo occurrence with confirmed paternity and maternity has been identified for NM_001127511.3:c.1636C>T in the available literature, ClinVar submissions, or exploratory search results. Details ▾Hide ▴
Evidence considered
- Systematic search of PubMed
- ClinVar
- and LOVD did not retrieve a confirmed de novo report for this variant
Still missing
- No de novo case with confirmed parentage identified
- large FAP registries may contain unreported de novo observations
PS3 No well-established functional study directly evaluating NM_001127511.3:c.1636C>T was identified. The APC VCEP PS3 rules require RNA assay evidence showing a premature stop codon or exon skipping, which has not been reported for this specific variant. The residue (Arg546) lies outside the β-catenin binding domain (codons 959-2129), so protein-level functional assays for β-catenin interaction are not applicable. Details ▾Hide ▴
Evidence considered
- No RNA assay or functional study evidence found for this variant
- Residue 546 is outside the β-catenin binding domain (codons 959-2129)
Still missing
- No variant-specific functional data available
Sources
PS4 ClinVar lists NM_001127511.3:c.1636C>T as Pathogenic with clinical laboratory submissions, but disaggregated case counts with phenotype points per the APC VCEP Table 1 are not available from the current evidence. The single individual in gnomAD v4.1 lacks phenotype annotation. Phenotype point scoring could not be completed. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Pathogenic (multiple clinical lab submissions)
- Insufficient phenotype-annotated case counts for VCEP Table 1 phenotype point scoring
Still missing
- Need phenotype-annotated proband counts for Table 1 scoring (polyposis phenotype
- CHRPE
- desmoid
- etc.)
- Clinical laboratory internal case counts not publicly accessible
Sources
PM6 No assumed de novo observation (without confirmation of paternity and maternity) has been identified for NM_001127511.3:c.1636C>T in the available literature, ClinVar submissions, or exploratory search results. Details ▾Hide ▴
Evidence considered
- Exploratory search did not identify any de novo report for this variant
Still missing
- No de novo observation with or without parentage confirmation identified
PP1 No co-segregation data has been identified for NM_001127511.3:c.1636C>T in the available literature or databases. The APC VCEP requires ≥3 meioses in ≥1 family for PP1_Supporting, which cannot be evaluated without family studies. Details ▾Hide ▴
Evidence considered
- No segregation studies found for this variant
Still missing
- No family-based segregation data available
BS2 No observation of NM_001127511.3:c.1636C>T in healthy individuals aged ≥50 years with documented absence of polyposis has been identified. The single allele in gnomAD v4.1 (NFE female) lacks phenotype annotation and does not meet the VCEP definition of a healthy individual (age ≥50, <5 adenomatous polyps, absence of Table 1 features). Details ▾Hide ▴
Evidence considered
- Single gnomAD v4.1 allele in NFE female
- no phenotype data available
- Cannot score as healthy individual under APC VCEP BS2 definition without clinical annotation
Still missing
- No phenotype-annotated healthy individual observations meeting VCEP criteria (age ≥50
- documented colonoscopy
- absence of FAP features)
Sources
BS3 BS3 under the APC VCEP requires RNA assay evidence showing no mRNA aberration or protein assay showing retention of wild-type function. NM_001127511.3:c.1636C>T is a nonsense variant predicted to undergo NMD, so BS3 would require experimental demonstration that the variant does NOT cause loss of function, which is biologically unlikely for a premature termination codon. No such evidence has been identified. Details ▾Hide ▴
Evidence considered
- No functional study evidence found showing retention of normal APC function for this variant
- Nonsense variants in APC are expected to result in LOF via NMD
Still missing
- No variant-specific functional data showing absence of deleterious effect
Sources
BS4 No evidence for lack of segregation of NM_001127511.3:c.1636C>T with FAP in affected family members has been identified. The APC VCEP requires affected members without the variant to score phenotype points per Table 1. Details ▾Hide ▴
Evidence considered
- No family studies with non-segregation data identified
Still missing
- No evidence of affected family members lacking the variant
BP2 No observation of NM_001127511.3:c.1636C>T in trans with a (likely) pathogenic APC variant has been reported. In a dominant tumor-suppressor disorder with severe phenotype, biallelic pathogenic APC variants would likely be lethal or result in an extremely severe phenotype, but formal documentation is absent. Details ▾Hide ▴
Evidence considered
- No trans observation with another pathogenic APC variant identified
- Biallelic APC LOF is expected to be severe/lethal
Still missing
- Formal documentation of lack of trans heterozygosity not available
BP5 No alternate genetic basis for the colorectal polyposis phenotype (e.g., pathogenic variants in MUTYH, NTHL1, MSH3, POLD1, POLE) has been documented in individuals carrying NM_001127511.3:c.1636C>T. BP5 requires identification of a (likely) pathogenic variant in another adenomatous polyposis gene. Details ▾Hide ▴
Evidence considered
- No alternate molecular diagnosis identified in individuals with this variant
Still missing
- No data on co-occurring variants in other polyposis genes
Not applicable · 11· recorded as not applicable Show reasons ▾Hide reasons ▴
PM1 VCEPPM1 is designated Not Applicable for APC by the ClinGen InSiGHT VCEP v2.1.0 based on current knowledge that no well-defined mutational hotspot or critical functional domain without benign variation has been established. Details ▾Hide ▴
PM5 N/APM5 requires a different missense change at the same amino acid residue as a known pathogenic missense variant. NM_001127511.3:c.1636C>T is a nonsense variant (p.Arg546Ter), not a missense change. The APC VCEP PM5 rule specifically addresses missense variants and Grantham distance comparisons, which are not applicable to stop-gain variants. Details ▾Hide ▴
Evidence considered
- Variant class is nonsense
- not missense
- pm5_candidates.json confirms: variant class is not missense-like
Sources
cspec ↗pm5_candidates
PP2 VCEPPP2 is designated Not Applicable for APC by the ClinGen InSiGHT VCEP v2.1.0 because missense variants are not a frequent mechanism of disease in APC; truncating variants are the predominant pathogenic mechanism. Details ▾Hide ▴
PP4 VCEPPP4 is designated Not Applicable for APC by the ClinGen InSiGHT VCEP v2.1.0. The VCEP specifies that the patient's phenotype and family history are already captured by the specifications of PS4 and PS5, so PP4 is not independently used. Details ▾Hide ▴
PP5 VCEPPP5 is designated Not Applicable for this VCEP as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee (Biesecker et al. 2018). Reputable source reporting alone is insufficient without independent evaluation of the underlying evidence. Details ▾Hide ▴
Evidence considered
- APC VCEP v2.1.0 specifies PP5 as Not Applicable per ClinGen SVI recommendations
Sources
BP1 N/ABP1 is applicable to missense variants in a gene where primarily truncating variants cause disease. NM_001127511.3:c.1636C>T is itself a truncating (nonsense) variant, not a missense variant. BP1 is not applicable to null variants that represent the primary disease mechanism. Details ▾Hide ▴
Evidence considered
- This is a nonsense (truncating) variant
- not a missense variant
- APC VCEP BP1 rule applies to missense variants with exception for β-catenin binding domain codons 1021-1035
Sources
BP3 VCEPSkipped per instructions: BP3 is not applicable for in-frame deletions/insertions in repetitive regions; this is a single-nucleotide substitution. Details ▾Hide ▴
No further detail was recorded.
BP4 N/AUnder the APC VCEP v2.1.0, BP4 is not applicable for missense variants and is intended for synonymous or intronic variants. NM_001127511.3:c.1636C>T is a nonsense variant in the coding region, which falls outside the scope of BP4. Details ▾Hide ▴
Evidence considered
- APC VCEP BP4 applies only to synonymous or intronic variants
- not nonsense variants
Sources
BP6 VCEPBP6 is designated Not Applicable for this VCEP as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Reputable source reporting alone is insufficient without independent evaluation of the underlying evidence. Details ▾Hide ▴
Evidence considered
- APC VCEP v2.1.0 specifies BP6 as Not Applicable per ClinGen SVI recommendations
Sources
BP7 N/ABP7 under the APC VCEP applies only to synonymous (silent) or intronic variants at or beyond +7/-21 positions where multiple splicing prediction algorithms predict no splice impact. NM_001127511.3:c.1636C>T is a nonsense (stop-gain) variant in the coding region, not a synonymous or intronic variant. Details ▾Hide ▴
Evidence considered
- BP7 is restricted to synonymous or intronic variants under APC VCEP v2.1.0
- This is a nonsense variant in the coding sequence
Sources
PS5 N/APS5 is not a recognized ACMG/AMP criterion. The closest criterion, PP5 (reputable source reports variant as pathogenic), is designated Not Applicable for this VCEP per ClinGen SVI recommendations. Details ▾Hide ▴
Evidence considered
- PS5 does not exist in the ACMG/AMP 2015 framework
- PP5 is not for use per the APC VCEP v2.1.0
Sources
Identifiers
- Gene
- APC
- Transcript
- NM_001127511.3
- Coding (HGVS c.)
- NM_001127511.3:c.1636C>T
- Protein (HGVS p.)
- NP_001120983.2:p.(Arg546Ter)
- GRCh38
- chr5:112828919 C>T
- GRCh37
- chr5:112164616 C>T
- ClinVar
- 1784452, 808
Gene diagram
Every interpreted variant in APC, mapped onto the exon structure of NM_001127511.3. Select a row to find it on the plot.
APCNM_001127511.3
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 APC
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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
1 / 1,613,730 alleles
AF 6.2e-07 · 0 homozygotes
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 6.2e-07 · 1 / 1,613,730 alleles · 0 hom
| European (non-Finnish)1 / 1,179,808 | 8.5e-07 |
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 6.19682e-07; MAF= 0.00006%, 1/1613730 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.47596e-07; MAF= 0.00008%, 1/1179808 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- 0.660
How the predictions were used
PP3 Under the APC VCEP v2.1.0, PP3 is applicable only to missense variants (via in silico splicing predictors to reveal possible splice effects) and non-canonical splicing variants. NM_001127511.3:c.1636C>T is a nonsense variant. SpliceAI predicts no significant splice impact (max delta score = 0.01). BayesDel score of 0.66 is not actionable under the VCEP PP3 rule, which prohibits use of conservation/evolutionary prediction models for missense variants and is silent on nonsense variants. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.01: no predicted splice impact
- BayesDel = 0.66
- but VCEP PP3 rule excludes conservation-based predictions
- PP3 is intended for missense and non-canonical splicing variants
- not nonsense variants
Sources
BP4 N/AUnder the APC VCEP v2.1.0, BP4 is not applicable for missense variants and is intended for synonymous or intronic variants. NM_001127511.3:c.1636C>T is a nonsense variant in the coding region, which falls outside the scope of BP4. Details ▾Hide ▴
Evidence considered
- APC VCEP BP4 applies only to synonymous or intronic variants
- not nonsense variants
Sources
BP7 N/ABP7 under the APC VCEP applies only to synonymous (silent) or intronic variants at or beyond +7/-21 positions where multiple splicing prediction algorithms predict no splice impact. NM_001127511.3:c.1636C>T is a nonsense (stop-gain) variant in the coding region, not a synonymous or intronic variant. Details ▾Hide ▴
Evidence considered
- BP7 is restricted to synonymous or intronic variants under APC VCEP v2.1.0
- This is a nonsense variant in the coding sequence
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). BayesDel score = 0.66.
9 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 11062151 ↗Expression of beta-catenin and full-length APC protein in normal and neoplastic colonic tissues.No paper-specific finding is recorded.
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PMID 11257105 ↗The ABC of APC.No paper-specific finding is recorded.
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PMID 15561772 ↗Truncating APC mutations have dominant effects on proliferation, spindle checkpoint control, survival and chromosome stability.No paper-specific finding is recorded.
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PMID 1324223 ↗Eight novel inactivating germ line mutations at the APC gene identified by denaturing gradient gel electrophoresis.Fodde R et al. · 1992No paper-specific finding is recorded.
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PMID 14523376 ↗Frequency and parental origin of de novo APC mutations in familial adenomatous polyposis.Aretz S et al. · 2004No paper-specific finding is recorded.
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PMID 15833136 ↗Rare mutations predisposing to familial adenomatous polyposis in Greek FAP patients.Mihalatos M et al. · 2005No paper-specific finding is recorded.
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PMID 23159591 ↗APC germline mutations in individuals being evaluated for familial adenomatous polyposis: a review of the Mayo Clinic experience with 1591 consecutive tests.Kerr SE et al. · 2013No paper-specific finding is recorded.
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PMID 24033266 ↗A systematic approach to assessing the clinical significance of genetic variants.No paper-specific finding is recorded.
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
1 / 1,613,730 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
16 Pathogenic · 1 Uncertain significance
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/1529292791
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/808/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/5-112164616-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr5-112828919-C-T?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_001127511.3%3Ac.1…
- OncoKB ↗www.oncokb.org/gene/APC/R546*
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=APC+c.1636C%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= 6.19682e-07; MAF= 0.00006%, 1/1613730 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.47596e-07; MAF= 0.00008%, 1/1179808 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
ClinVar
Error retrieving ClinVar entry.
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). BayesDel score = 0.66.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
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.