About BRIP1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRIP1 c.254C>T, p.(Ser85Leu)
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
NM_032043.3:c.254C>T is present at extremely low frequency in population databases: gnomAD v2.1 AF=1.19e-5 (3/251,440 alleles), gnomAD v4.1 AF=9.91e-6 (16/1,613,990 alleles), gnomAD-Canada absent. Both frequencies are well below the 0.1% PM2 threshold for a rare variant in a gene associated with dominant disease.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest NM_032043.3:c.254C>T does not impact gene product function. REVEL score is 0.078 (strongly benign-leaning, threshold for pathogenic is >0.5). BayesDel score is -0.316 (negative, indicating benign). SpliceAI max delta is 0.03 (no predicted splicing impact). These concordant predictions from independent algorithms support a benign interpretation.
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, BP4 supporting benign; combination = 1 supporting + 1 supporting benign, which maps to VUS.
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
16 / 1,613,990 alleles
gnomAD v4.1: 16 / 1,613,990 alleles. Recorded AF 9.91332e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.19313e-05; MAF= 0.00119%, 3/251440 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.63773e-05; MAF= 0.00264%, 3/113734 alleles, homozygotes = 0); grpmax FAF= 7.01e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.030 maximum delta
Recorded SpliceAI maximum delta score: 0.030. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
14 reported laboratory submissions
13 Uncertain significance · 1 Uncertain Significance. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BRIP1, a DEAH helicase, is altered by mutation and amplification in various cancers, including breast cancer and melanoma.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
1 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV113270205, n = 1 times).
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.
27 criteria with recorded statuses: 2 met · 20 not met · 0 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_032043.3:c.254C>T (p.Ser85Leu) is a missense variant in BRIP1. PVS1 does not apply as this is not a null variant.
This variant is present at extremely low frequency in population databases: gnomAD v2.1 at 0.00119% (3/251,440 alleles) and gnomAD v4.1 at 0.00099% (16/1,613,990 alleles), with no homozygotes observed. This meets the PM2 criterion at supporting strength for a rare variant in a gene associated with dominant cancer predisposition.
Multiple in silico prediction tools support a benign effect: REVEL score 0.078 (strongly benign-leaning), BayesDel score -0.316 (benign), and SpliceAI max delta 0.03 (no predicted splicing impact). These concordant predictions meet BP4 at supporting benign strength.
No functional studies have directly tested p.Ser85Leu. The largest BRIP1 missense functional characterization study (PMID:31822495) tested 20 helicase domain variants but did not include this residue. OncoKB reports no variant-specific functional evidence.
ClinVar classifies this variant as Uncertain Significance (Variation ID: 141545) with 1-star review status based on 14 clinical laboratory submissions. No expert panel classification is available. This does not meet criteria for PP5 or BP6 application.
No case-control studies, cosegregation data, de novo reports, or same-residue pathogenic comparators are available. BRIP1 missense variants in the helicase domain are a known disease mechanism (PMID:31822495), so BP1 does not apply despite this being a missense change.
The combined evidence (PM2 supporting + BP4 supporting benign) yields conflicting benign and pathogenic signals. The overall classification is Variant of Uncertain Significance (VUS), consistent with the ClinVar consensus.
No criteria match.
Met · 2
PM2 SupportingNM_032043.3:c.254C>T is present at extremely low frequency in population databases: gnomAD v2.1 AF=1.19e-5 (3/251,440 alleles), gnomAD v4.1 AF=9.91e-6 (16/1,613,990 alleles), gnomAD-Canada absent. Both frequencies are well below the 0.1% PM2 threshold for a rare variant in a gene associated with dominant disease. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 3/251
- 440 alleles (0.00119%)
- gnomAD v4.1: 16/1
- 613
- 990 alleles (0.00099%)
- absent from gnomAD-Canada
- zero homozygotes in all datasets.
Sources
BP4 SupportingMultiple lines of computational evidence suggest NM_032043.3:c.254C>T does not impact gene product function. REVEL score is 0.078 (strongly benign-leaning, threshold for pathogenic is >0.5). BayesDel score is -0.316 (negative, indicating benign). SpliceAI max delta is 0.03 (no predicted splicing impact). These concordant predictions from independent algorithms support a benign interpretation. Details ▾Hide ▴
Evidence considered
- REVEL: 0.078 (benign)
- BayesDel: -0.316 (benign)
- SpliceAI max delta: 0.03 (no splicing impact). Three independent algorithms concur on benign.
Sources
Not met · 20 · evaluated, threshold not reached
PS1 No different amino acid change at codon 85 has been established as pathogenic. PM5 candidate search found zero same-residue comparator variants in ClinVar. Details ▾Hide ▴
Evidence considered
- No pathogenic variant at the same codon identified in ClinVar or literature.
Sources
pm5_candidatesclinvar ↗
PS2 No de novo occurrence of NM_032043.3:c.254C>T has been reported in any reviewed publication or ClinVar submission. Parental confirmation is absent. Details ▾Hide ▴
Evidence considered
- No de novo observation in ClinVar submissions or reviewed literature.
Sources
PS3 No functional studies have directly tested NM_032043.3:c.254C>T (p.Ser85Leu). The BRIP1 missense functional characterization study (PMID:31822495) tested 20 variants in the helicase domain but did not include p.Ser85Leu. No systematic range characterization (tiling screen, saturation mutagenesis) covers position 85. OncoKB reports no variant-specific functional evidence. Details ▾Hide ▴
Evidence considered
- PMID:31822495 tested 20 BRIP1 missense variants but did not include p.Ser85Leu. OncoKB classification is Unknown Oncogenic Effect with no variant-specific evidence.
Still missing
- No functional data available for p.Ser85Leu.
Sources
PS4 No case-control studies demonstrate statistically significant enrichment of NM_032043.3:c.254C>T in affected individuals. The variant is observed in gnomAD at low frequency (3/251,440 alleles v2.1; 16/1,613,990 alleles v4.1), and no published prevalence data distinguish carrier frequency in cases versus controls. Details ▾Hide ▴
Evidence considered
- Present in gnomAD population databases at very low frequency. No case-control enrichment data.
Still missing
- No case-control study or cohort enrichment analysis available.
Sources
PM1 While p.Ser85Leu lies within the BRIP1 helicase domain (aa 1-888), a well-established functional domain, cancerhotspots.org does not identify this residue as a statistically significant mutational hotspot. The variant is present at very low frequency in population databases, and no domain-specific constraint or functional data demonstrate that position 85 is critical for protein function. Without a residue-specific hotspot or domain-level mutational constraint data, PM1 cannot be applied. Details ▾Hide ▴
Evidence considered
- Residue 85 is within the helicase domain but is not a statistically significant hotspot per cancerhotspots.org. The 31822495 paper characterizes the helicase domain generally but does not test position 85.
Still missing
- No domain-level constraint or saturation mutagenesis data for the region containing residue 85.
Sources
PM5 No different missense change at codon 85 has been classified as pathogenic in ClinVar. The PM5 candidate search returned zero same-residue comparator variants. PM5 requires a pathogenic missense variant at the same amino acid residue. Details ▾Hide ▴
Evidence considered
- Zero same-residue pathogenic comparator variants identified in ClinVar.
Sources
pm5_candidatesclinvar ↗
PM6 No de novo occurrence of NM_032043.3:c.254C>T has been reported, with or without confirmed parentage. No ClinVar submission asserts de novo origin. Details ▾Hide ▴
Evidence considered
- No de novo assertion in any ClinVar submission or reviewed publication.
Sources
PP1 No cosegregation data are available for NM_032043.3:c.254C>T. No family studies with this variant have been published or included in ClinVar submissions. Details ▾Hide ▴
Evidence considered
- No segregation or family study data available.
Still missing
- No family-based segregation analysis.
Sources
PP2 PP2 requires a gene with a low rate of benign missense variation where missense variants are a common disease mechanism. While BRIP1 missense variants can be pathogenic (PMID:31822495 demonstrated ~75% of tested helicase domain missense variants impair function), no gene-level constraint metric (e.g., missense Z-score, gnomAD constraint) was available to confirm a low rate of benign missense variation. HCI prior was not available for BRIP1. Details ▾Hide ▴
Evidence considered
- BRIP1 missense variants can impair function (PMID:31822495)
- but gene-level constraint metrics confirming low benign missense variation rate are not available.
Still missing
- No gene-level missense constraint metric (Z-score
- LOEUF) available.
Sources
PP3 Multiple in silico prediction tools support a benign effect for NM_032043.3:c.254C>T. REVEL score is 0.078 (well below the 0.5 threshold for pathogenicity). BayesDel score is -0.316 (negative score indicates benign). SpliceAI max delta is 0.03 (no predicted splicing impact). No computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.078 (benign)
- BayesDel: -0.316 (benign)
- SpliceAI max delta: 0.03 (no splicing impact).
Sources
PP4 No specific patient phenotype or family history data are available to evaluate. BRIP1-associated cancer phenotypes (breast and ovarian cancer) are not highly specific for a single genetic etiology. Clinical testing submissions report this variant as VUS without phenotype specificity. Details ▾Hide ▴
Evidence considered
- Cancer phenotypes associated with BRIP1 are not highly specific. No patient-level phenotype data reviewed.
Still missing
- No patient phenotype data available for review.
Sources
PP5 ClinVar classifies NM_032043.3:c.254C>T as Uncertain Significance (Variation ID: 141545) with review status 'criteria provided, single submitter' (1 star). No expert panel (3-star) classification exists. PP5 requires a reputable source reporting the variant as pathogenic, which is not met. Details ▾Hide ▴
Evidence considered
- ClinVar: Uncertain significance
- 1-star review status
- 14 clinical laboratory submissions.
Sources
BA1 gnomAD allele frequency is 0.00119% (v2.1) and 0.00099% (v4.1), well below the 1% BA1 threshold. This variant is not common enough in population databases to be considered a benign polymorphism. Details ▾Hide ▴
Evidence considered
- Maximum gnomAD AF: 0.00119% (v2.1)
- far below the 1% BA1 threshold.
Sources
BS1 gnomAD allele frequency is 0.00119% (v2.1) and 0.00099% (v4.1), below the 0.3% BS1 threshold. The variant is too rare in population databases to apply BS1. Details ▾Hide ▴
Evidence considered
- Maximum gnomAD AF: 0.00119% (v2.1)
- below the 0.3% BS1 threshold.
Sources
BS2 BS2 requires observation in a healthy adult individual for a disorder with full penetrance expected at an early age. While 3 alleles are observed in gnomAD v2.1 and 16 in v4.1, gnomAD does not confirm these individuals are healthy adults. Furthermore, BRIP1-associated cancer risk is adult-onset with moderate/incomplete penetrance, making the healthy-adult observation framework difficult to apply without explicit phenotype confirmation. Details ▾Hide ▴
Evidence considered
- Variant observed in gnomAD but no confirmed healthy adult phenotype data. BRIP1 cancer risk is adult-onset with incomplete penetrance.
Still missing
- No confirmed healthy adult carriers with phenotype data.
Sources
BS3 No functional studies demonstrate that NM_032043.3:c.254C>T (p.Ser85Leu) does not impair protein function. The BRIP1 functional study (PMID:31822495) tested 20 missense variants but did not include p.Ser85Leu. In silico predictors (REVEL 0.078, BayesDel -0.316) suggest a benign effect, but computational prediction alone is insufficient for BS3 which requires experimental functional evidence. Details ▾Hide ▴
Evidence considered
- No experimental functional data available for p.Ser85Leu. In silico scores suggest benign but are insufficient for BS3.
Still missing
- No direct functional characterization of p.Ser85Leu.
Sources
BP1 BP1 applies when a missense variant occurs in a gene where primarily truncating variants cause disease. In BRIP1, missense variants in the helicase domain are a known disease mechanism: PMID:31822495 demonstrated that ~75% (15/20) of tested missense variants in the helicase domain significantly impair interstrand crosslink repair. Therefore, missense variation in BRIP1 cannot be assumed benign. Details ▾Hide ▴
Evidence considered
- PMID:31822495 shows ~75% of tested BRIP1 helicase domain missense variants are loss-of-function
- missense is a known disease mechanism in BRIP1.
Sources
BP2 No evidence that NM_032043.3:c.254C>T has been observed in trans with a pathogenic variant for a fully penetrant dominant disorder, or in cis with a pathogenic variant. No such data are available. Details ▾Hide ▴
BP5 BP5 requires the variant to be found in a case with an alternate molecular basis for disease. No such data are available for NM_032043.3:c.254C>T. Details ▾Hide ▴
Evidence considered
- No observation of this variant in a case with an alternate molecular diagnosis.
Still missing
- No co-occurrence data with other pathogenic variants.
Sources
BP6 ClinVar classifies NM_032043.3:c.254C>T as Uncertain Significance (Variation ID: 141545, 1-star review). BP6 requires a reputable source to report the variant as benign, which is not met. Details ▾Hide ▴
Evidence considered
- ClinVar classification is Uncertain significance
- not benign. 1-star review status.
Sources
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_032043.3:c.254C>T is a missense variant (p.Ser85Leu), not a null variant (nonsense, frameshift, or canonical splice site). PVS1 does not apply to missense substitutions under the ClinGen SVI PVS1 decision framework (PMC6185798). Details ▾Hide ▴
Evidence considered
- Missense substitution at codon 85
- variant bucket is 'other'
- generic PVS1 framework not applicable.
Sources
BS4 N/ANo family segregation data are available for this variant. BS4 requires observation of nonsegregation with disease in affected family members, which cannot be evaluated. Details ▾Hide ▴
Evidence considered
- No segregation or family data available for review.
BP3 N/ABP3 applies to in-frame deletions or insertions in repetitive regions without known function. NM_032043.3:c.254C>T is a missense substitution, not an in-frame indel. Details ▾Hide ▴
Evidence considered
- Variant is a substitution
- not an in-frame indel.
BP7 N/ABP7 applies to synonymous variants with no predicted splicing impact. NM_032043.3:c.254C>T is a missense variant (p.Ser85Leu), not a synonymous change. Details ▾Hide ▴
Evidence considered
- Variant is missense
- not synonymous.
PS5 N/APS5 is not defined in the standard ACMG/AMP 2015 framework used for this generic assessment. No CSPEC/VCEP framework is available for BRIP1 that defines this criterion. Details ▾Hide ▴
Evidence considered
- Standard ACMG/AMP 2015 criteria do not include PS5.
Sources
generic_acmg_combination_rulesfinal_classification_framework
Identifiers
- Gene
- BRIP1
- Transcript
- NM_032043.3
- Coding (HGVS c.)
- NM_032043.3:c.254C>T
- Protein (HGVS p.)
- NP_114432.2:p.(Ser85Leu)
- GRCh38
- chr17:61857183 G>A
- GRCh37
- chr17:59934544 G>A
- ClinVar
- 141545
- COSMIC
- COSV113270205
Gene diagram
Every interpreted variant in BRIP1, mapped onto the exon structure of NM_032043.3. Select a row to find it on the plot.
BRIP1NM_032043.3
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 BRIP1
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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
16 / 1,613,990 alleles
AF 9.91e-06 · 0 homozygotes · FAF 6.88e-06
gnomAD v2.1
3 / 251,440 alleles
AF 1.19e-05 · 0 homozygotes · FAF 7.01e-06
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 9.9e-06 · 16 / 1,613,990 alleles · 0 hom · FAF 6.9e-06
| Remaining individuals2 / 62,486 | 3.2e-05 |
| European (non-Finnish)14 / 1,179,970 | 1.2e-05 |
0 alternate alleles recorded in 8 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 1.2e-05 · 3 / 251,440 alleles · 0 hom · FAF 7e-06
| European (non-Finnish)3 / 113,734 | 2.6e-05 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 9.91332e-06; MAF= 0.00099%, 16/1613990 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 3.20072e-05; MAF= 0.00320%, 2/62486 alleles, homozygotes = 0); grpmax FAF= 6.88e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.19313e-05; MAF= 0.00119%, 3/251440 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.63773e-05; MAF= 0.00264%, 3/113734 alleles, homozygotes = 0); grpmax FAF= 7.01e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.078
- BayesDel
- -0.316
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest NM_032043.3:c.254C>T does not impact gene product function. REVEL score is 0.078 (strongly benign-leaning, threshold for pathogenic is >0.5). BayesDel score is -0.316 (negative, indicating benign). SpliceAI max delta is 0.03 (no predicted splicing impact). These concordant predictions from independent algorithms support a benign interpretation. Details ▾Hide ▴
Evidence considered
- REVEL: 0.078 (benign)
- BayesDel: -0.316 (benign)
- SpliceAI max delta: 0.03 (no splicing impact). Three independent algorithms concur on benign.
Sources
PP3 Multiple in silico prediction tools support a benign effect for NM_032043.3:c.254C>T. REVEL score is 0.078 (well below the 0.5 threshold for pathogenicity). BayesDel score is -0.316 (negative score indicates benign). SpliceAI max delta is 0.03 (no predicted splicing impact). No computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.078 (benign)
- BayesDel: -0.316 (benign)
- SpliceAI max delta: 0.03 (no splicing impact).
Sources
BP7 N/ABP7 applies to synonymous variants with no predicted splicing impact. NM_032043.3:c.254C>T is a missense variant (p.Ser85Leu), not a synonymous change. Details ▾Hide ▴
Evidence considered
- Variant is missense
- not synonymous.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.078. BayesDel score = -0.316079.
10 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.Richards S et al. · 2015ACMG/AMP standards and guidelines for the interpretation of sequence variants. Provides the framework for variant classification but does not discuss BRIP1 or NM_032043.3:c.254C>T.Does not name this variant
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PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.Describes a standardized DNA variant scoring system for Mendelian disorders. Does not discuss BRIP1 or NM_032043.3:c.254C>T.Does not name this variant
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PMID 26901136 ↗Identification of Novel Candidate Genes for Early-Onset Colorectal Cancer Susceptibility.de Voer RM et al. · 2016Identifies PTPN12 and LRP6 as candidate early-onset colorectal cancer susceptibility genes through whole-exome sequencing. BRIP1 is listed once as a gene with a potentially pathogenic variant in S5 Table, but NM_032043.3:c.254C>T is not specified or discussed.Does not name this variant
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PMID 31822495 ↗Rare BRIP1 Missense Alleles Confer Risk for Ovarian and Breast Cancer.Moyer CL et al. · 2020Functionally characterized 20 rare BRIP1 missense variants in the helicase domain for interstrand crosslink repair activity. Demonstrated ~75% of tested variants are loss-of-function. Tested variants include P47A, A349P, A745T, D791V, Y822H, E636K, E511G, G690E, Q740H, I691L, and others, but p.Ser85Leu was not among the variants tested.Does not name this variant
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PMID 20301575 ↗Fanconi Anemia.Adam MP et al. · 1993GeneReview on Fanconi Anemia, covering multiple FA genes including BRIP1 (FANCJ). General clinical resource; does not discuss NM_032043.3:c.254C>T.Does not name this variant
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PMID 26389210 ↗Genetics of Breast and Gynecologic Cancers (PDQ®): Health Professional Version.PDQ cancer genetics summary on breast and gynecologic cancers. General clinical resource; does not discuss NM_032043.3:c.254C>T.Does not name this variant
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PMID 26921362 ↗No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.Easton DF et al. · 2016Study examining whether protein truncating variants in BRIP1 are associated with breast cancer risk. Concluded no evidence for association of BRIP1 truncating variants with breast cancer. This variant is a missense change, not a truncating variant, and the specific variant is not discussed.Does not name this variant
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PMID 29450531 ↗Screening for Ovarian Cancer: US Preventive Services Task Force Recommendation Statement.US Preventive Services Task Force et al. · 2018USPSTF recommendation statement on screening for ovarian cancer. Public health screening guideline; does not discuss BRIP1 variants.Does not name this variant
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PMID 22964825 ↗Screening for ovarian cancer: U.S. Preventive Services Task Force reaffirmation recommendation statement.Moyer VA et al. · 2012USPSTF reaffirmation recommendation on ovarian cancer screening. Does not discuss BRIP1 or 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 refinement of ACMG-AMP variant classification criteria. Methodology paper; does not discuss NM_032043.3:c.254C>T.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
16 / 1,613,990 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.030
Open source ↗
ClinVar
13 Uncertain significance · 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 ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/141545/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-59934544-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-61857183-G-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/17-61857183-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_032043.3%3Ac.254C…
- OncoKB ↗www.oncokb.org/gene/BRIP1/S85L
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=123806080
- 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= 9.91332e-06; MAF= 0.00099%, 16/1613990 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 3.20072e-05; MAF= 0.00320%, 2/62486 alleles, homozygotes = 0); grpmax FAF= 6.88e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.19313e-05; MAF= 0.00119%, 3/251440 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.63773e-05; MAF= 0.00264%, 3/113734 alleles, homozygotes = 0); grpmax FAF= 7.01e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (13 clinical laboratories) and as Uncertain Significance (1 clinical laboratory). (ClinVarID = 141545)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.078. BayesDel score = -0.316079.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BRIP1, a DEAH helicase, is altered by mutation and amplification in various cancers, including breast cancer and melanoma.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV113270205, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.