About BRIP1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRIP1 c.736A>G, p.(Ile246Val)
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 very low frequency in population databases. gnomAD v2.1 overall AF=0.01553% (39/251,202 alleles, 0 homozygotes), grpmax FAF=0.09%. gnomAD v4.1 overall AF=0.00700% (113/1,613,894 alleles, 0 homozygotes), grpmax FAF=0.087%. All frequencies are below the 0.1% PM2 threshold for non-VCEP assessment.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.197 (below pathogenic threshold), BayesDel score is -0.206707 (benign-leaning), and SpliceAI predicts no splicing alteration (max delta 0.04). The concordance of multiple in silico tools predicting a benign effect meets BP4 at supporting strength.
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; 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
113 / 1,613,894 alleles
gnomAD v4.1: 113 / 1,613,894 alleles. Recorded AF 7.0017e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000155254; MAF= 0.01553%, 39/251202 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.00120868; MAF= 0.12087%, 37/30612 alleles, homozygotes = 0); grpmax FAF= 0.00090082.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI score
0.040 maximum delta
Recorded SpliceAI maximum delta score: 0.040. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
9 reported laboratory submissions
5 Uncertain significance · 4 Likely benign. ClinVar API review status: criteria provided, conflicting classifications.
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
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.
29 criteria with recorded statuses: 2 met · 22 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.736A>G (p.Ile246Val) in BRIP1 is a missense variant assessed under generic ACMG/AMP 2015 framework. No CSPEC/VCEP framework exists for BRIP1.
This variant is present at very low frequency in gnomAD (v2.1 AF=0.01553%, grpmax FAF=0.09%; v4.1 AF=0.00700%, grpmax FAF=0.087%) with no homozygotes, meeting PM2 at supporting strength.
Multiple in silico tools predict a benign effect: REVEL score 0.197, BayesDel score -0.206707, and SpliceAI predicts no splicing alteration (max delta 0.04), meeting BP4 at supporting strength.
ClinVar reports this variant as Uncertain significance by 5 clinical laboratories and Likely benign by 4 clinical laboratories (VariationID 461180). No expert panel classification is available. The ClinVar review status is 1-star and does not meet thresholds for PP5 or BP6.
No functional studies, segregation data, case-control data, or de novo observations were identified for this variant. Full-text review of three available publications (PMID:25741868, PMID:26467025, PMID:29641532) confirmed none mention NM_032043.3:c.736A>G.
The only applicable criteria are PM2 (supporting pathogenic) and BP4 (supporting benign). With one supporting pathogenic and one supporting benign criterion, the variant defaults to Uncertain Significance (VUS) under the ACMG/AMP 2015 scoring framework.
No criteria match.
Met · 2
PM2 SupportingThis variant is present at very low frequency in population databases. gnomAD v2.1 overall AF=0.01553% (39/251,202 alleles, 0 homozygotes), grpmax FAF=0.09%. gnomAD v4.1 overall AF=0.00700% (113/1,613,894 alleles, 0 homozygotes), grpmax FAF=0.087%. All frequencies are below the 0.1% PM2 threshold for non-VCEP assessment. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF=0.01553%
- grpmax FAF=0.09%
- 0 homozygotes. gnomAD v4.1: AF=0.00700%
- grpmax FAF=0.087%
- 0 homozygotes.
Sources
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.197 (below pathogenic threshold), BayesDel score is -0.206707 (benign-leaning), and SpliceAI predicts no splicing alteration (max delta 0.04). The concordance of multiple in silico tools predicting a benign effect meets BP4 at supporting strength. Details ▾Hide ▴
Evidence considered
- REVEL=0.197 (benign)
- BayesDel=-0.206707 (benign)
- SpliceAI delta=0.04 (no effect). Concordant benign predictions from multiple in silico tools.
Sources
Not met · 22 · evaluated, threshold not reached
PS1 No prior pathogenic nucleotide change at the same amino acid position (p.Ile246) was identified in ClinVar or other curated sources. A different nucleotide change leading to the same missense change is required for PS1. Details ▾Hide ▴
Evidence considered
- No alternate nucleotide substitution at codon 246 reported as pathogenic in ClinVar.
Sources
PS2 No de novo confirmation data are available for this variant. PS2 requires confirmed de novo occurrence with maternity and paternity confirmed. Details ▾Hide ▴
Evidence considered
- No de novo reports identified.
Still missing
- No parental testing data available.
PS3 No functional studies were identified for NM_032043.3:c.736A>G (p.Ile246Val) or for a systematically characterized range that includes this residue. OncoKB reports 'Unknown Oncogenic Effect' with no curated PMIDs. One ClinVar submitter (Color Diagnostics) explicitly stated functional studies have not been reported for this variant. Details ▾Hide ▴
Evidence considered
- OncoKB: Unknown Oncogenic Effect
- no functional PMIDs. Color Diagnostics submission (SCV000684301): 'to our knowledge
- functional studies have not been reported for this variant.'
Still missing
- No functional assay data for this variant or a systematically characterized range encompassing residue 246.
Sources
PS4 No case-control prevalence data comparing affected individuals to controls are available for this variant. PS4 requires statistically significant enrichment in affected individuals over controls. Details ▾Hide ▴
Evidence considered
- No case-control or cohort prevalence data identified for this variant.
Still missing
- No case-control frequency data available.
PM1 Residue p.Ile246 does not lie within a statistically significant mutational hotspot (cancerhotspots.org) and no residue-specific functional domain characterization was identified in the case materials to support PM1 at domain level. Details ▾Hide ▴
Evidence considered
- Cancerhotspots.org: residue not significant
- exact variant not listed.
Still missing
- No domain-level functional characterization linking residue 246 to a well-defined critical domain.
PM5 No pathogenic missense variant at the same codon (p.Ile246) with a different amino acid change was identified in ClinVar. Automated PM5 candidate harvesting was unable to confirm classic same-residue semantics. Details ▾Hide ▴
Evidence considered
- PM5 candidate search: 0 same-residue pathogenic comparators found.
Sources
pm5_candidates
PM6 No de novo data are available. PM6 requires a confirmed de novo observation with maternity and paternity confirmed, without confirmation of paternity and maternity. Details ▾Hide ▴
Evidence considered
- No de novo reports identified.
Still missing
- No parental testing data available.
PP1 No co-segregation data in multiple affected family members are available for this variant. Details ▾Hide ▴
Evidence considered
- No segregation data identified.
Still missing
- No family segregation data available.
PP2 Insufficient constraint data are available to determine whether BRIP1 has a low rate of benign missense variation. PP2 requires a gene-specific missense Z-score or equivalent constraint metric demonstrating intolerance to missense variation. Details ▾Hide ▴
Evidence considered
- No gene-level missense constraint data available in the case materials.
Still missing
- Missense constraint metrics (e.g.
- gnomAD missense Z-score) not available for BRIP1 in the case materials.
PP3 Multiple in silico tools predict no damaging effect. REVEL score is 0.197 (below the 0.5 pathogenic threshold), BayesDel score is -0.206707 (benign-leaning), and SpliceAI max delta is 0.04 (no predicted splice impact). These results do not support a deleterious prediction. Details ▾Hide ▴
Evidence considered
- REVEL=0.197 (not deleterious)
- BayesDel=-0.206707 (benign)
- SpliceAI delta=0.04 (no splice impact).
Sources
PP4 No patient phenotype or family history data specific to this variant are available. PP4 requires a phenotype or family history highly specific for a disease with a single genetic etiology. Details ▾Hide ▴
Evidence considered
- No phenotype or family history data available.
Still missing
- Individual-level phenotype data not available.
PP5 ClinVar classification for this variant is 'Uncertain significance' (5 clinical laboratories) and 'Likely benign' (4 clinical laboratories) with review status 'criteria provided, single submitter' (1-star). No expert panel (3-star) classification as pathogenic exists. The ClinVar evidence does not meet PP5 threshold requiring a reputable source to classify as pathogenic. Details ▾Hide ▴
Evidence considered
- ClinVar VariationID 461180: 5 labs VUS
- 4 labs Likely benign
- review status 1-star
- 0 expert panel submissions.
Sources
BA1 The highest observed population frequency is 0.12% in South Asian (gnomAD v2.1 SAS), which is well below the 1% BA1 threshold. No population exceeds the BA1 cutoff. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 SAS AF=0.12%
- gnomAD v4.1 SAS AF=0.10%
- both <1% BA1 threshold.
Sources
BS1 The highest observed population frequency is 0.12% in South Asian (gnomAD v2.1 SAS), which is below the 0.3% BS1 threshold for non-VCEP assessment. No population exceeds the BS1 cutoff. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 SAS AF=0.12%
- gnomAD v4.1 SAS AF=0.10%
- both <0.3% BS1 threshold.
Sources
BS2 No homozygous observations are recorded in gnomAD (0 homozygotes in both v2.1 and v4.1). BS2 requires observation in a homozygous state or in trans with a known pathogenic variant in a gene with a recessive disorder, or observation in a healthy adult for a fully penetrant dominant disorder. Details ▾Hide ▴
BS3 No functional studies demonstrating no damaging effect on protein function or splicing were identified for this variant. OncoKB reports no curated functional evidence, and full-text review of available publications found no variant-specific functional data. Details ▾Hide ▴
Evidence considered
- No functional assay data identified. In silico alone (REVEL
- BayesDel) does not constitute BS3.
Still missing
- No experimental functional studies available.
Sources
BS4 No segregation data showing lack of co-segregation with disease are available for this variant. Details ▾Hide ▴
Evidence considered
- No segregation data available.
Still missing
- No family segregation data available.
BP1 Although BRIP1 loss-of-function is a supported disease mechanism, BRIP1 is not a gene for which primarily truncating variants are known to cause disease. Pathogenic missense variants are also reported in BRIP1. BP1 requires the gene to have a disease mechanism primarily driven by truncating variants. Details ▾Hide ▴
Evidence considered
- BRIP1 LOF mechanism supported
- but pathogenic missense variants are also established
- not a truncating-only disease gene.
Sources
pvs1_gene_context
BP2 No observation of this variant in trans with a known pathogenic variant in a fully penetrant dominant disorder was identified. Details ▾Hide ▴
Evidence considered
- No co-occurrence data with known pathogenic variants available.
BP5 No observation of this variant in a case with an alternate molecular basis for disease was identified. BP5 requires the variant to be found in a case with a clear alternate genetic cause. Details ▾Hide ▴
Evidence considered
- No case with alternate molecular basis identified.
BP6 ClinVar classification includes 4 clinical laboratories reporting 'Likely benign,' but the review status is 'criteria provided, single submitter' (1-star). No expert panel (3-star) classification as benign or likely benign exists. The BP6 threshold requiring a reputable source to classify as benign is not met. Details ▾Hide ▴
Evidence considered
- ClinVar VariationID 461180: 4 labs Likely benign
- but review status 1-star
- 0 expert panel submissions.
Sources
PS5 No reputable source has recently reported this variant as pathogenic without access to the underlying evidence. ClinVar classification is 'Uncertain significance' or 'Likely benign' across all submissions. Details ▾Hide ▴
Evidence considered
- ClinVar: 5 labs classify as Uncertain significance
- 4 labs as Likely benign
- no pathogenic classification.
Sources
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_032043.3:c.736A>G (p.Ile246Val) is a missense variant and does not fall into the generic PVS1 null-variant buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants per ClinGen SVI PVS1 recommendations (PMC6185798). Details ▾Hide ▴
PM3 N/AThis variant is being assessed for a dominant disorder framework; PM3 (in trans with a pathogenic variant for recessive disorders) is not applicable. Details ▾Hide ▴
No further detail was recorded.
PM4 N/AThis variant is a substitution (missense), not a protein-length-altering change (in-frame deletion/insertion or stop-loss). Details ▾Hide ▴
No further detail was recorded.
BP3 N/AThis variant is a substitution, not an in-frame deletion or insertion in a repetitive region without a known function. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ANM_032043.3:c.736A>G (p.Ile246Val) is a missense variant, not a synonymous variant. BP7 is only applicable to synonymous variants without predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 applies only to synonymous variants.
Identifiers
- Gene
- BRIP1
- Transcript
- NM_032043.3
- Coding (HGVS c.)
- NM_032043.3:c.736A>G
- Protein (HGVS p.)
- NP_114432.2:p.(Ile246Val)
- GRCh38
- chr17:61808649 T>C
- GRCh37
- chr17:59886010 T>C
- ClinVar
- 461180
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
113 / 1,613,894 alleles
AF 7e-05 · 0 homozygotes · FAF 0.000873
gnomAD v2.1
39 / 251,202 alleles
AF 0.000155 · 0 homozygotes · FAF 0.000901
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 7e-05 · 113 / 1,613,894 alleles · 0 hom · FAF 0.00087
| South Asian95 / 91,084 | 0.001 |
| Middle Eastern1 / 6,080 | 0.00016 |
| Admixed American4 / 60,000 | 6.7e-05 |
| Remaining individuals1 / 62,488 | 1.6e-05 |
| European (non-Finnish)12 / 1,179,922 | 1e-05 |
0 alternate alleles recorded in 5 other groups: European (Finnish), Amish, East Asian, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 0.00016 · 39 / 251,202 alleles · 0 hom · FAF 0.0009
| South Asian37 / 30,612 | 0.0012 |
| Remaining individuals1 / 6,126 | 0.00016 |
| European (non-Finnish)1 / 113,514 | 8.8e-06 |
0 alternate alleles recorded in 5 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish).
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 7.0017e-05; MAF= 0.00700%, 113/1613894 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.00104299; MAF= 0.10430%, 95/91084 alleles, homozygotes = 0); grpmax FAF= 0.00087265.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000155254; MAF= 0.01553%, 39/251202 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.00120868; MAF= 0.12087%, 37/30612 alleles, homozygotes = 0); grpmax FAF= 0.00090082.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.197
- BayesDel
- -0.207
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.197 (below pathogenic threshold), BayesDel score is -0.206707 (benign-leaning), and SpliceAI predicts no splicing alteration (max delta 0.04). The concordance of multiple in silico tools predicting a benign effect meets BP4 at supporting strength. Details ▾Hide ▴
Evidence considered
- REVEL=0.197 (benign)
- BayesDel=-0.206707 (benign)
- SpliceAI delta=0.04 (no effect). Concordant benign predictions from multiple in silico tools.
Sources
PP3 Multiple in silico tools predict no damaging effect. REVEL score is 0.197 (below the 0.5 pathogenic threshold), BayesDel score is -0.206707 (benign-leaning), and SpliceAI max delta is 0.04 (no predicted splice impact). These results do not support a deleterious prediction. Details ▾Hide ▴
Evidence considered
- REVEL=0.197 (not deleterious)
- BayesDel=-0.206707 (benign)
- SpliceAI delta=0.04 (no splice impact).
Sources
BP7 N/ANM_032043.3:c.736A>G (p.Ile246Val) is a missense variant, not a synonymous variant. BP7 is only applicable to synonymous variants without predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 applies only to synonymous variants.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.04). REVEL score = 0.197. BayesDel score = -0.206707.
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 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.ACMG/AMP standards and guidelines for the interpretation of sequence variants. This is the foundational framework document for variant classification. The specific variant NM_032043.3:c.736A>G is not discussed.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. Over 16,500 pathogenicity assessments across 338 genes were analyzed for scoring rule development. The specific variant NM_032043.3:c.736A>G is not discussed.Does not name this variant
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PMID 28796317 ↗Mutation status of RAD51C, PALB2 and BRIP1 in 100 Japanese familial breast cancer cases without BRCA1 and BRCA2 mutations.Sato K et al. · 2017Analyzed mutation status of RAD51C, PALB2, and BRIP1 in 100 Japanese familial breast cancer cases without BRCA1/BRCA2 mutations. The abstract does not list specific BRIP1 variants identified; the variant NM_032043.3:c.736A>G was not mentioned in the available abstract.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. · 2004National Society of Genetic Counselors practice recommendations for cancer genetic risk assessment and counseling. This is a clinical practice guideline; no specific variants are discussed.Does not name this variant
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PMID 24366376 ↗Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement.Moyer VA et al. · 2014U.S. Preventive Services Task Force recommendation statement on BRCA-related cancer risk assessment and genetic testing. This is a screening guideline; no specific variants are discussed.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. This is a clinical referral guideline; no specific variants are discussed.Does not name this variant
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PMID 26389258 ↗Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional VersiPDQ cancer genetics risk assessment and counseling summary (Health Professional Version). This is a clinical summary resource; no abstract or full text was retrievable for variant review.Does not name this variant
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PMID 29641532 ↗Germline mutations in candidate predisposition genes in individuals with cutaneous melanoma and at least two independent additional primary cancers.Pritchard AL et al. · 2018Investigated germline mutations in cancer predisposition genes in individuals with cutaneous melanoma and multiple primary cancers. BRIP1 was among the genes screened, but NM_032043.3:c.736A>G (p.Ile246Val) was not identified in the full text of this publication.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. This is a variant classification methodology paper describing the Sherloc system. No specific BRIP1 variants are discussed.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
113 / 1,613,894 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.040
Open source ↗
ClinVar
5 Uncertain significance · 4 Likely 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/461180/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-59886010-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-61808649-T-C?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/17-61808649-T-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_032043.3%3Ac.736A…
- OncoKB ↗www.oncokb.org/gene/BRIP1/I246V
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRIP1+c.736A%3EG
- 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= 7.0017e-05; MAF= 0.00700%, 113/1613894 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.00104299; MAF= 0.10430%, 95/91084 alleles, homozygotes = 0); grpmax FAF= 0.00087265.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000155254; MAF= 0.01553%, 39/251202 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.00120868; MAF= 0.12087%, 37/30612 alleles, homozygotes = 0); grpmax FAF= 0.00090082.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (5 clinical laboratories) and as Likely benign (4 clinical laboratories). (ClinVarID = 461180)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.04). REVEL score = 0.197. BayesDel score = -0.206707.
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 not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.