About BRCA1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA1 c.2155A>G, p.(Lys719Glu)
Classification
Benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A 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 BRCA1 VCEP v1.2.0. 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: 0
Benign evidence criteria: 4
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 4
BS1Strong
BS1 · strong
This variant exceeds the ENIGMA BS1 threshold for benign population frequency. The grpmax FAF is 0.00062195 in gnomAD v2.1 and 0.00068503 in gnomAD v4.1, both above the BS1 cutoff of 0.0001 and below the BA1 cutoff of 0.001.
BP1Strong
BP1 · strong
This is a missense variant outside the BRCA1 clinically important functional domains used by the ENIGMA framework, and SpliceAI predicts no splice effect with a max delta score of 0.00. These findings meet BP1_Strong for a missense change outside a critical domain without predicted splicing impact.
BP5Strong
BP5 · strong
Available multifactorial clinical-history evidence supports a benign direction. The BRCA1 clinical-history likelihood ratio is 0.0137 from 10 probands, which is below the BP5_Strong threshold of 0.05 and above the Very Strong threshold of 0.00285, so BP5_Strong is met.
BP6Supporting
BP6 · supporting
Expert panel ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen classified as Benign.
Recorded classification: Benign
ENIGMA BRCA1/BRCA2 Specification v1.2 Table 3 final-classification framework (CSPEC/VCEP override)
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
67 / 1,614,060 alleles
gnomAD v4.1: 67 / 1,614,060 alleles. Recorded AF 4.15102e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.0823e-05; MAF= 0.00708%, 20/282394 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000803277; MAF= 0.08033%, 20/24898 alleles, homozygotes = 0); grpmax FAF= 0.00062195.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
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. BRCA1, a tumor suppressor involved in the DNA damage response, is mutated in various cancer types.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
Not assessed
No COSMIC evidence statement is recorded in this case.
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen BRCA1 VCEP v1.2.0, with the data and sources behind each one.
28 criteria with recorded statuses: 4 met · 4 not met · 8 not assessed · 12 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The BRCA1 NM_007294.3:c.2155A>G (NP_009225.1:p.(Lys719Glu), NP_009225.1:p.(K719E)) variant has not been observed in COSMIC and has been reported in ClinVar with a current expert-panel Benign classification, although older laboratory submissions include uncertain significance and likely benign assertions.
This variant is present in population databases, including gnomAD v2.1 and v4.1, with grpmax FAF values of 0.00062195 and 0.00068503, respectively, which are above the ENIGMA BS1 threshold of 0.0001 but below the BA1 threshold of 0.001.
Multifactorial clinical-history evidence is in the benign direction, with a BRCA1 clinical-history likelihood ratio of 0.0137 from 10 probands, meeting BP5_Strong and arguing against pathogenicity.
In silico evidence does not support a damaging effect in the ENIGMA BRCA1 framework: SpliceAI predicts no splice impact (max delta score 0.00), BayesDel is -0.216062, and the missense change lies outside the BRCA1 domains used for PP3/BP4, supporting BP1_Strong rather than PP3.
No criteria match.
Met · 4
BS1 StrongThis variant exceeds the ENIGMA BS1 threshold for benign population frequency. The grpmax FAF is 0.00062195 in gnomAD v2.1 and 0.00068503 in gnomAD v4.1, both above the BS1 cutoff of 0.0001 and below the BA1 cutoff of 0.001. Details ▾Hide ▴
Rule
ENIGMA BS1_Strong applies when FAF >0.0001 in a non-founder population.
Evidence considered
- gnomAD v2.1 grpmax FAF 0.00062195.
- gnomAD v4.1 grpmax FAF 0.00068503.
Sources
BP1 StrongThis is a missense variant outside the BRCA1 clinically important functional domains used by the ENIGMA framework, and SpliceAI predicts no splice effect with a max delta score of 0.00. These findings meet BP1_Strong for a missense change outside a critical domain without predicted splicing impact. Details ▾Hide ▴
Rule
ENIGMA BP1_Strong applies to missense variants outside defined functional domains with SpliceAI ≤0.1.
Evidence considered
- Protein change p.Lys719Glu lies outside BRCA1 RING aa 2-101
- coiled-coil aa 1391-1424
- and BRCT aa 1650-1857.
- SpliceAI max delta score 0.00.
Sources
BP5 StrongAvailable multifactorial clinical-history evidence supports a benign direction. The BRCA1 clinical-history likelihood ratio is 0.0137 from 10 probands, which is below the BP5_Strong threshold of 0.05 and above the Very Strong threshold of 0.00285, so BP5_Strong is met. Details ▾Hide ▴
Rule
ENIGMA BP5_Strong applies when multifactorial LR ≤0.05 against pathogenicity.
Evidence considered
- Clinical-history LR 0.01373116940682096 for c.2155A>G with 10 probands.
Sources
Not met · 4 · evaluated, threshold not reached
PM2 This variant is not absent from population databases. It is present in gnomAD v2.1 at AF 0.0000708 with African/African American AF 0.000803 and grpmax FAF 0.00062195, and in gnomAD v4.1 at AF 0.0000415 with African/African American AF 0.000853 and grpmax FAF 0.00068503; therefore the ENIGMA requirement for absence from controls is not met. Details ▾Hide ▴
Rule
ENIGMA PM2_Supporting requires absence from gnomAD controls.
Evidence considered
- gnomAD v2.1 total AF 7.0823e-05
- grpmax FAF 0.00062195.
- gnomAD v4.1 total AF 4.15102e-05
- grpmax FAF 0.00068503.
Sources
PP3 Computational evidence does not meet the BRCA1 ENIGMA PP3 rule. The variant is outside the specified clinically important BRCA1 domains, BayesDel is -0.216062 which is below the PP3 threshold of 0.28, SpliceAI shows no predicted splice effect with max delta score 0.00, and REVEL is 0.404 but REVEL is not the governing ENIGMA threshold for BRCA1 PP3. Details ▾Hide ▴
Rule
ENIGMA PP3 for BRCA1 missense variants requires location in a defined functional domain with BayesDel ≥0.28, or predicted splice impact with SpliceAI ≥0.2.
Evidence considered
- BayesDel no-AF score -0.216062.
- SpliceAI max delta score 0.00.
- REVEL score 0.404.
- Variant position p.Lys719Glu is outside BRCA1 RING
- coiled-coil
- and BRCT domains used for PP3/BP4 logic.
Sources
PP4 Available multifactorial clinical-history evidence is in the benign direction rather than the pathogenic direction. The BRCA1 clinical-history likelihood ratio is 0.0137 from 10 probands, which is well below the PP4 threshold of 2.08 and therefore does not support PP4. Details ▾Hide ▴
Rule
ENIGMA PP4 requires multifactorial LR ≥2.08 toward pathogenicity.
Evidence considered
- Clinical-history LR 0.01373116940682096 for c.2155A>G with 10 probands.
Sources
BA1 The population frequency does not reach the ENIGMA BA1 threshold. The highest observed grpmax FAF is 0.00068503 in gnomAD v4.1, which is below the BA1 cutoff of 0.001. Details ▾Hide ▴
Rule
ENIGMA BA1 requires FAF >0.001.
Evidence considered
- gnomAD v4.1 grpmax FAF 0.00068503.
- gnomAD v2.1 grpmax FAF 0.00062195.
Sources
Not assessed · 8 · no assessment recorded
PS3 No variant-specific calibrated functional study showing a damaging effect was identified in the available evidence, so PS3 cannot be applied at this time. Details ▾Hide ▴
Rule
ENIGMA PS3 requires well-established variant-specific functional evidence supportive of a damaging effect.
Evidence considered
- OncoKB did not identify variant-specific reviewed functional evidence.
- No exact c.2155A>G entry was identified in the reviewed ENIGMA Table 9 lookup.
Still missing
- No exact-variant calibrated protein or combined RNA/protein functional result was identified in the available evidence.
Sources
PS4 No case-control or enrichment data showing this variant is significantly more common in affected individuals than in controls were identified, so PS4 was not applied. Details ▾Hide ▴
Rule
ENIGMA PS4 requires significant enrichment in affected individuals over controls.
Evidence considered
- ClinVar shows mixed historical submissions with current expert-panel Benign classification
- but no case-control enrichment evidence.
Still missing
- No exact-variant odds ratio or case-control dataset was identified.
Sources
PM3 No evidence was identified that this variant was observed with a second BRCA1 pathogenic variant in a patient with BRCA1-related Fanconi anemia, so PM3 was not applied. Details ▾Hide ▴
Rule
ENIGMA PM3 requires biallelic BRCA1 disease-context evidence.
Evidence considered
- PM3 in ENIGMA BRCA1 is limited to recessive Fanconi anemia context.
Still missing
- No Fanconi anemia proband-level biallelic data were identified.
Sources
PP1 No segregation data were identified for this variant, so PP1 cannot be applied. Details ▾Hide ▴
BS2 No proband-level evidence was identified to score absence of BRCA1-related Fanconi anemia features, so BS2 was not applied. Details ▾Hide ▴
Rule
ENIGMA BS2 requires point-based evidence from individuals lacking recessive disease features.
Evidence considered
- BS2 in ENIGMA BRCA1 requires proband-level scoring in the recessive disease context.
Still missing
- No case-level point-based BS2 evidence was identified.
Sources
BS3 No variant-specific calibrated functional study showing no damaging effect was identified in the available evidence, so BS3 cannot be applied at this time. Details ▾Hide ▴
Rule
ENIGMA BS3 requires well-established variant-specific functional evidence supportive of no damaging effect.
Evidence considered
- OncoKB did not identify variant-specific reviewed functional evidence.
- No exact c.2155A>G entry was identified in the reviewed ENIGMA Table 9 lookup.
Still missing
- No exact-variant calibrated benign functional assay result was identified in the available evidence.
Sources
BS4 No lack-of-segregation data were identified for this variant, so BS4 was not applied. Details ▾Hide ▴
BP7 No RNA study demonstrating a normal transcript profile for this variant was identified, so BP7 was not applied. Details ▾Hide ▴
Rule
ENIGMA BP7 for missense variants requires transcript-level evidence when used in this context.
Evidence considered
- SpliceAI predicts no splice impact
- but ENIGMA BP7 for missense variants requires RNA evidence for normal transcript effect.
Still missing
- No exact-variant mRNA assay result was identified.
Sources
Not applicable · 12· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis missense variant does not fall within the BRCA1 ENIGMA loss-of-function categories for PVS1. It is not a nonsense, frameshift, canonical ±1/2 splice, initiation-codon, or exon-level deletion variant, and SpliceAI does not predict an abnormal splice effect (max delta score 0.00). Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 PVS1 applies to null variants or RNA-proven loss-of-function events, not to this missense substitution without predicted splice impact.
Evidence considered
- BRCA1 ENIGMA PVS1 framework is applicable at the gene level
- but this variant is a missense substitution outside the default null-variant buckets.
- SpliceAI max delta score is 0.00.
Sources
PS1 N/AAvailable evidence did not identify a separate pathogenic nucleotide change producing the same amino acid substitution. This amino acid change is generated by the observed codon-level substitution itself, so PS1 is not supported here. Details ▾Hide ▴
Rule
ENIGMA PS1 requires a previously classified pathogenic or likely pathogenic variant with the same protein or splicing consequence.
Evidence considered
- ClinVar contains this exact variant as Benign by expert panel review.
- No alternate same-amino-acid pathogenic comparator was identified in the available evidence.
Sources
PS2 VCEPNo de novo framework is used for BRCA1 in this ENIGMA specification. Details ▾Hide ▴
VCEP rule
Not applicable in ENIGMA BRCA1 v1.2.
Evidence considered
- CSPEC lists PS2 as not applicable.
Sources
PM1 VCEPPM1 is not used in this BRCA1 ENIGMA framework for this variant context. Details ▾Hide ▴
VCEP rule
Not applicable in ENIGMA BRCA1 v1.2.
Evidence considered
- CSPEC lists PM1 as not applicable.
Sources
PM4 VCEPPM4 is not applicable because this is not a protein length-changing in-frame variant or stop-loss variant, and the ENIGMA BRCA1 specification marks PM4 as not applicable. Details ▾Hide ▴
VCEP rule
Not applicable in ENIGMA BRCA1 v1.2.
Evidence considered
- CSPEC lists PM4 as not applicable.
Sources
PM5 N/AIn this BRCA1 ENIGMA framework, PM5 is repurposed for truncating or protein-termination-codon logic and not for classic same-residue missense comparison. Because this variant is a missense substitution, PM5 is not applicable. Details ▾Hide ▴
Rule
ENIGMA BRCA1 PM5 applies to qualifying PTC variants, not this missense variant.
Evidence considered
- PM5 candidate review flagged BRCA1 PM5 mode as PTC-specific and not eligible for classic same-residue missense use.
Sources
cspec ↗pm5_candidates
PM6 VCEPNo de novo framework is used for BRCA1 in this ENIGMA specification. Details ▾Hide ▴
VCEP rule
Not applicable in ENIGMA BRCA1 v1.2.
Evidence considered
- CSPEC lists PM6 as not applicable.
Sources
PP2 VCEPPP2 is not used in this BRCA1 ENIGMA framework. Details ▾Hide ▴
VCEP rule
Not applicable in ENIGMA BRCA1 v1.2.
Evidence considered
- CSPEC lists PP2 as not applicable.
Sources
PP5 VCEPPP5 is not used in this BRCA1 ENIGMA framework. Details ▾Hide ▴
VCEP rule
Not applicable in ENIGMA BRCA1 v1.2.
Evidence considered
- CSPEC lists PP5 as not applicable.
Sources
BP2 VCEPBP2 is not used in this BRCA1 ENIGMA framework. Details ▾Hide ▴
VCEP rule
Not applicable in ENIGMA BRCA1 v1.2.
Evidence considered
- CSPEC lists BP2 as not applicable.
Sources
BP3 VCEPBP3 is not used in this BRCA1 ENIGMA framework. Details ▾Hide ▴
VCEP rule
Not applicable in ENIGMA BRCA1 v1.2.
Evidence considered
- CSPEC lists BP3 as not applicable.
Sources
BP4 N/ABP4 is not the appropriate benign computational rule for this missense variant because the BRCA1 ENIGMA specification restricts BP4 missense use to variants inside defined clinically important domains with BayesDel no-AF ≤0.15 and SpliceAI ≤0.1. This variant is outside those domains, so benign computational support is captured by BP1 instead. Details ▾Hide ▴
Rule
ENIGMA BP4 missense use is limited to variants inside defined functional domains.
Evidence considered
- Variant is outside the BRCA1 domains specified for BP4.
- BayesDel no-AF score -0.216062.
- SpliceAI max delta score 0.00.
Sources
Identifiers
- Gene
- BRCA1
- Transcript
- NM_007294.3
- Coding (HGVS c.)
- NM_007294.3:c.2155A>G
- Protein (HGVS p.)
- NP_009225.1:p.(Lys719Glu)
- GRCh38
- chr17:43093376 T>C
- GRCh37
- chr17:41245393 T>C
- ClinVar
- 2752887, 1788885, 845101, 441436, 141804, 91581, 37465, 37461, 37452
Gene diagram
Every interpreted variant in BRCA1, mapped onto the exon structure of NM_007294.3. Select a row to find it on the plot.
BRCA1NM_007294.3
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 BRCA1
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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
67 / 1,614,060 alleles
AF 4.15e-05 · 0 homozygotes · FAF 0.000685
gnomAD v2.1
20 / 282,394 alleles
AF 7.08e-05 · 0 homozygotes · FAF 0.000622
By genetic ancestry
gnomAD v4.1
AF 4.2e-05 · 67 / 1,614,060 alleles · 0 hom · FAF 0.00069
| African/African American64 / 75,066 | 0.00085 |
| Remaining individuals3 / 62,506 | 4.8e-05 |
0 alternate alleles recorded in 8 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, European (non-Finnish).
gnomAD v2.1
AF 7.1e-05 · 20 / 282,394 alleles · 0 hom · FAF 0.00062
| African/African American20 / 24,898 | 0.0008 |
0 alternate alleles recorded in 7 other groups: Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 4.15102e-05; MAF= 0.00415%, 67/1614060 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000852583; MAF= 0.08526%, 64/75066 alleles, homozygotes = 0); grpmax FAF= 0.00068503.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.0823e-05; MAF= 0.00708%, 20/282394 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000803277; MAF= 0.08033%, 20/24898 alleles, homozygotes = 0); grpmax FAF= 0.00062195.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.404
- BayesDel
- -0.216
How the predictions were used
PP3 Computational evidence does not meet the BRCA1 ENIGMA PP3 rule. The variant is outside the specified clinically important BRCA1 domains, BayesDel is -0.216062 which is below the PP3 threshold of 0.28, SpliceAI shows no predicted splice effect with max delta score 0.00, and REVEL is 0.404 but REVEL is not the governing ENIGMA threshold for BRCA1 PP3. Details ▾Hide ▴
Rule
ENIGMA PP3 for BRCA1 missense variants requires location in a defined functional domain with BayesDel ≥0.28, or predicted splice impact with SpliceAI ≥0.2.
Evidence considered
- BayesDel no-AF score -0.216062.
- SpliceAI max delta score 0.00.
- REVEL score 0.404.
- Variant position p.Lys719Glu is outside BRCA1 RING
- coiled-coil
- and BRCT domains used for PP3/BP4 logic.
Sources
BP7 No RNA study demonstrating a normal transcript profile for this variant was identified, so BP7 was not applied. Details ▾Hide ▴
Rule
ENIGMA BP7 for missense variants requires transcript-level evidence when used in this context.
Evidence considered
- SpliceAI predicts no splice impact
- but ENIGMA BP7 for missense variants requires RNA evidence for normal transcript effect.
Still missing
- No exact-variant mRNA assay result was identified.
Sources
BP4 N/ABP4 is not the appropriate benign computational rule for this missense variant because the BRCA1 ENIGMA specification restricts BP4 missense use to variants inside defined clinically important domains with BayesDel no-AF ≤0.15 and SpliceAI ≤0.1. This variant is outside those domains, so benign computational support is captured by BP1 instead. Details ▾Hide ▴
Rule
ENIGMA BP4 missense use is limited to variants inside defined functional domains.
Evidence considered
- Variant is outside the BRCA1 domains specified for BP4.
- BayesDel no-AF score -0.216062.
- SpliceAI max delta score 0.00.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.404. BayesDel score = -0.216062.
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
-
PMID 15385441 ↗Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition.Pavlicek A et al. · 2004No paper-specific finding is recorded.
-
PMID 16267036 ↗Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations.Judkins T et al. · 2005No paper-specific finding is recorded.
-
PMID 23918944 ↗Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.No paper-specific finding is recorded.
-
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.No paper-specific finding is recorded.
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PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.No paper-specific finding is recorded.
-
PMID 31911673 ↗Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots".No paper-specific finding is recorded.
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PMID 10923033 ↗The breast cancer information core: database design, structure, and scope.Szabo C et al. · 2000No paper-specific finding is recorded.
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PMID 15604628 ↗Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.No paper-specific finding is recorded.
-
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
67 / 1,614,060 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
Captured ClinVar source record
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/1530970787
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/37452/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-41245393-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-43093376-T-C?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_007294.3%3Ac.2155…
- OncoKB ↗www.oncokb.org/gene/BRCA1/K719E
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA1+c.2155A%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= 4.15102e-05; MAF= 0.00415%, 67/1614060 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000852583; MAF= 0.08526%, 64/75066 alleles, homozygotes = 0); grpmax FAF= 0.00068503.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.0823e-05; MAF= 0.00708%, 20/282394 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000803277; MAF= 0.08033%, 20/24898 alleles, homozygotes = 0); grpmax FAF= 0.00062195.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (7 clinical laboratories) and as Likely benign (7 clinical laboratories) and as Likely Benign (1 clinical laboratory) and as Benign by ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 37452)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.404. BayesDel score = -0.216062.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BRCA1, a tumor suppressor involved in the DNA damage response, is mutated in various cancer types.
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.