About BRCA1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA1 c.1568T>G, p.(Leu523Trp)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen 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: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
The variant is absent from gnomAD v2.1 (non-cancer, exome only subset), meeting the ENIGMA PM2_Supporting criterion for absence from controls in an outbred population. In gnomAD v4.1, a single allele is observed (AF = 6.2e-7, 1/1,613,758 alleles, no homozygotes).
Benign criteria applied · 1
BP1Strong
BP1 · strong
This missense variant lies outside ENIGMA-defined clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857) and no splicing impact is predicted (SpliceAI max delta = 0.00, ≤0.1). The variant falls within the BRCA1 exon 11 coldspot region (aa 224-1366), where no pathogenic missense variants have been reported. Per ENIGMA rules, BP1_Strong applies.
Recorded classification: Likely benign
Conflicting evidence: PM2_Supporting (+1 pathogenic) and BP1_Strong (-4 benign) both met. Applied ENIGMA BRCA1 v1.2.0 conflicting-evidence point system. Total = -3, which falls in the Likely Benign range (-6 to -2).
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 / 1,613,758 alleles
gnomAD v4.1: 1 / 1,613,758 alleles. Recorded AF 6.19672e-07. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
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
7 reported laboratory submissions
6 Uncertain significance · 1 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. 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
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 BRCA1 VCEP v1.2.0, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 14 not met · 0 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_007294.3:c.1568T>G (p.Leu523Trp) is a missense variant in BRCA1 exon 10, located outside the clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857).
This variant is absent from gnomAD v2.1 (non-cancer exome subset) and present at extremely low frequency in gnomAD v4.1 (1/1,613,758 alleles; AF = 6.20e-7). The absence from the v2.1 outbred population controls meets ENIGMA PM2_Supporting.
The variant falls within the BRCA1 exon 11 coldspot region (aa 224-1366), where no pathogenic missense variants have been observed in ClinVar. Combined with its location outside clinically important functional domains and absence of predicted splicing impact (SpliceAI = 0.00), this meets ENIGMA BP1_Strong.
In silico predictors are discordant: BayesDel (0.322, ≥0.28 threshold) predicts a damaging protein change but PP3 is not triggered because the variant lies outside clinically important functional domains per ENIGMA rules. REVEL score is 0.613.
No functional data (PS3/BS3), segregation data (PP1/BS4), clinical-history likelihood ratios (PP4/BP5), or case-control studies (PS4) are available for this variant. It is absent from the ENIGMA Table 9 curated functional assay results and from the ST4 functional assay dataset.
The variant is reported in ClinVar as Uncertain significance by 6 clinical laboratories and Likely benign by 1 laboratory (ClinVar ID 54295). No expert panel classification is available.
With PM2_Supporting on the pathogenic side and BP1_Strong on the benign side, the evidence is conflicting and does not meet ENIGMA Table 3 thresholds for Likely Pathogenic, Likely Benign, or Benign classification. The variant remains classified as Uncertain Significance.
No criteria match.
Met · 2
PM2 SupportingThe variant is absent from gnomAD v2.1 (non-cancer, exome only subset), meeting the ENIGMA PM2_Supporting criterion for absence from controls in an outbred population. In gnomAD v4.1, a single allele is observed (AF = 6.2e-7, 1/1,613,758 alleles, no homozygotes). Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (non-cancer exome subset).
- One allele in gnomAD v4.1 (AF = 6.20e-7).
Sources
BP1 StrongThis missense variant lies outside ENIGMA-defined clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857) and no splicing impact is predicted (SpliceAI max delta = 0.00, ≤0.1). The variant falls within the BRCA1 exon 11 coldspot region (aa 224-1366), where no pathogenic missense variants have been reported. Per ENIGMA rules, BP1_Strong applies. Details ▾Hide ▴
Evidence considered
- Position 523 is outside functional domains (RING 2-101
- coiled-coil 1391-1424
- BRCT 1650-1857).
- SpliceAI max delta = 0.00 (≤0.1
- no splicing predicted).
- Exon 11 coldspot with 0 P/LP missense variants (PMID:31911673).
Sources
Not met · 14 · evaluated, threshold not reached
PS1 No previously classified pathogenic or likely pathogenic missense variant at the same amino acid position (Leu523) with a different substitution has been identified in the ENIGMA specification tables, ClinVar, or the reviewed literature. Details ▾Hide ▴
Evidence considered
- No pathogenic comparator at codon 523 identified in ENIGMA Table 9 or ClinVar.
Sources
PS3 No variant-specific or systematic-range functional data is available for NM_007294.3:c.1568T>G. The variant is absent from ENIGMA Table 9 (pre-assigned PS3/BS3 codes) and absent from the ST4 functional assay results in SupplementaryTables. No functional study mentioning this variant was identified in the reviewed literature. Details ▾Hide ▴
Evidence considered
- Absent from ENIGMA Table 9 (curated functional assay results).
- Absent from ST4 functional assay dataset (Findlay 2018
- Fernandes 2019
- Bouwman 2020).
PS4 No case-control study demonstrating statistically significant enrichment of this variant in affected individuals versus controls has been identified. The ENIGMA specification requires p-value ≤0.05 and OR ≥4 with lower CI excluding 2.0. Details ▾Hide ▴
Evidence considered
- No case-control data available for this variant.
PP1 No co-segregation data are available for this variant. No family studies with quantitative co-segregation analysis were identified in the reviewed literature. Details ▾Hide ▴
Evidence considered
- No segregation data available.
PP3 Although BayesDel (0.322, ≥0.28 threshold) predicts a damaging protein change, the variant lies outside ENIGMA-defined clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857). Per ENIGMA PP3 rules, PP3 requires both BayesDel ≥0.28 AND location inside a clinically important functional domain for missense variants. SpliceAI delta score is 0.00 (<0.2), so the splicing-based PP3 rule does not apply. Details ▾Hide ▴
Evidence considered
- BayesDel = 0.322 (≥0.28
- predicted damaging).
- Position 523 is outside clinically important functional domains.
- SpliceAI max delta = 0.00 (<0.2
- no predicted splicing).
Sources
PP4 The variant is not listed in the Li et al. 2020 (PMID:31853058) BRCA1 clinical-history likelihood ratio table. No clinical-history LR is available for PP4 assignment under ENIGMA rules. Details ▾Hide ▴
Evidence considered
- Absent from Li et al. 2020 BRCA1 clinical-history LR table.
Sources
BA1 The variant does not meet ENIGMA BA1 threshold (filter allele frequency >0.1% in gnomAD v2.1 or v3.1). The variant is absent from gnomAD v2.1 and present at extremely low frequency in v4.1 (AF = 6.2e-7). Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1.
- gnomAD v4.1 AF = 6.20e-7
- far below BA1 threshold of >0.001.
Sources
BS1 The variant does not meet ENIGMA BS1 thresholds. BS1_Strong requires FAF >0.0001 (0.01%) and BS1_Supporting requires FAF >0.00002 (0.002%) and ≤0.0001 in gnomAD v2.1 or v3.1. The variant is absent from v2.1 and has AF = 6.2e-7 in v4.1, below both thresholds. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1.
- gnomAD v4.1 AF = 6.20e-7
- below BS1_Supporting threshold of 2e-5.
Sources
BS2 No observation of this variant in a healthy adult individual without features of Fanconi anemia has been identified in the available evidence. ENIGMA BS2 requires proband-level data showing absence of recessive disease phenotype. Details ▾Hide ▴
Evidence considered
- No proband-level data available for BS2 assessment.
BS3 No well-established functional study demonstrates absence of a damaging effect for this variant. The variant is absent from ENIGMA Table 9 (pre-assigned BS3 codes) and absent from the ST4 functional assay results. No functional study showing benign effect was identified in the reviewed literature. Details ▾Hide ▴
Evidence considered
- Absent from ENIGMA Table 9 (curated functional assay results).
- Absent from ST4 functional assay dataset.
BS4 No lack-of-segregation data are available for this variant. No cosegregation analysis was identified in the reviewed literature. Details ▾Hide ▴
Evidence considered
- No segregation data available.
BP4 The ENIGMA BP4 rule applies only to missense variants inside a clinically important functional domain with no predicted impact (BayesDel ≤0.15 AND SpliceAI ≤0.1), or to intronic variants outside donor/acceptor sites. This missense variant lies outside the defined functional domains, and BayesDel (0.322) exceeds the BP4 threshold of ≤0.15, so BP4 is not applicable under ENIGMA rules. Details ▾Hide ▴
Evidence considered
- Variant is outside clinically important functional domains.
- BayesDel = 0.322 (>0.15 BP4 threshold).
Sources
BP5 The variant is not listed in the Li et al. 2020 (PMID:31853058) BRCA1 clinical-history likelihood ratio table. No clinical-history LR is available for BP5 assignment under ENIGMA rules. Details ▾Hide ▴
Evidence considered
- Absent from Li et al. 2020 BRCA1 clinical-history LR table.
Sources
BP7 BP7_Strong (RNA) requires well-established mRNA assay data showing no damaging effect on splicing. Although SpliceAI predicts no splicing impact (delta = 0.00), SpliceAI alone is not a functional assay and no mRNA transcript analysis data are available for this variant. BP7_Supporting applies only to silent or intronic variants meeting BP4, which does not apply here. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00 (predictive only
- not functional assay).
- No mRNA transcript analysis data available.
Sources
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_007294.3:c.1568T>G is a missense variant (p.Leu523Trp), not a null variant (nonsense, frameshift, or canonical ±1,2 splice site). PVS1 is restricted to null variants under the ENIGMA BRCA1 specification. Details ▾Hide ▴
No further detail was recorded.
PS2 VCEPPS2 is designated Not Applicable by the ENIGMA BRCA1 specification v1.2.0. Details ▾Hide ▴
PM1 VCEPPM1 is designated Not Applicable by the ENIGMA BRCA1 specification v1.2.0. Additionally, amino acid position 523 lies outside the ENIGMA-defined clinically important functional domains (RING: aa 2-101, coiled-coil: aa 1391-1424, BRCT: aa 1650-1857). Position 523 falls within the exon 11 coldspot region (aa 224-1366) where no pathogenic missense variants have been reported. Details ▾Hide ▴
Evidence considered
- ENIGMA CSPEC marks PM1 as Not Applicable.
- Position 523 is in BRCA1 exon 11 coldspot (PMID:31911673).
Sources
PM5 N/AUnder the ENIGMA BRCA1 specification, PM5 is repurposed for protein termination codon (PTC) variants only (PM5_PTC), applied when a PTC occurs in an exon where a proven pathogenic PTC has been observed. NM_007294.3:c.1568T>G is a missense variant, not a PTC. Classic same-residue missense PM5 also does not apply: no pathogenic missense variant at codon 523 has been identified. Details ▾Hide ▴
Evidence considered
- ENIGMA PM5 is PTC-specific
- variant is missense.
- No pathogenic missense comparator at codon 523.
Sources
PM6 VCEPPM6 is designated Not Applicable by the ENIGMA BRCA1 specification v1.2.0. Details ▾Hide ▴
PP2 VCEPPP2 is designated Not Applicable by the ENIGMA BRCA1 specification v1.2.0. Details ▾Hide ▴
PP5 VCEPPP5 is designated Not Applicable by the ENIGMA BRCA1 specification v1.2.0. Details ▾Hide ▴
BP2 VCEPBP2 is designated Not Applicable by the ENIGMA BRCA1 specification v1.2.0. Details ▾Hide ▴
BP6 VCEPBP6 is designated Not Applicable by the ENIGMA BRCA1 specification v1.2.0. Details ▾Hide ▴
PS5 N/APS5 is designated Not Applicable by the ENIGMA BRCA1 specification v1.2.0. The variant is classified in ClinVar as Uncertain significance, not as Pathogenic by any reputable source. Details ▾Hide ▴
Identifiers
- Gene
- BRCA1
- Transcript
- NM_007294.3
- Coding (HGVS c.)
- NM_007294.3:c.1568T>G
- Protein (HGVS p.)
- NP_009225.1:p.(Leu523Trp)
- GRCh38
- chr17:43093963 A>C
- GRCh37
- chr17:41245980 A>C
- ClinVar
- 868877, 868449, 867858, 864939, 825350, 819888, 631339, 479216, 462636, 55456
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
1 / 1,613,758 alleles
AF 6.2e-07 · 0 homozygotes
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 6.2e-07 · 1 / 1,613,758 alleles · 0 hom
| European (non-Finnish)1 / 1,179,912 | 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.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 6.19672e-07; MAF= 0.00006%, 1/1613758 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.47521e-07; MAF= 0.00008%, 1/1179912 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.613
- BayesDel
- 0.323
How the predictions were used
PP3 Although BayesDel (0.322, ≥0.28 threshold) predicts a damaging protein change, the variant lies outside ENIGMA-defined clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857). Per ENIGMA PP3 rules, PP3 requires both BayesDel ≥0.28 AND location inside a clinically important functional domain for missense variants. SpliceAI delta score is 0.00 (<0.2), so the splicing-based PP3 rule does not apply. Details ▾Hide ▴
Evidence considered
- BayesDel = 0.322 (≥0.28
- predicted damaging).
- Position 523 is outside clinically important functional domains.
- SpliceAI max delta = 0.00 (<0.2
- no predicted splicing).
Sources
BP4 The ENIGMA BP4 rule applies only to missense variants inside a clinically important functional domain with no predicted impact (BayesDel ≤0.15 AND SpliceAI ≤0.1), or to intronic variants outside donor/acceptor sites. This missense variant lies outside the defined functional domains, and BayesDel (0.322) exceeds the BP4 threshold of ≤0.15, so BP4 is not applicable under ENIGMA rules. Details ▾Hide ▴
Evidence considered
- Variant is outside clinically important functional domains.
- BayesDel = 0.322 (>0.15 BP4 threshold).
Sources
BP7 BP7_Strong (RNA) requires well-established mRNA assay data showing no damaging effect on splicing. Although SpliceAI predicts no splicing impact (delta = 0.00), SpliceAI alone is not a functional assay and no mRNA transcript analysis data are available for this variant. BP7_Supporting applies only to silent or intronic variants meeting BP4, which does not apply here. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00 (predictive only
- not functional assay).
- No mRNA transcript analysis data available.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.613. BayesDel score = 0.322592.
9 paper records listed. 1 cited in the classification. None of the listed paper records explicitly indicates that the variant is named.
Cited in the classification
-
PMID 31911673 ↗Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots".Identifies coldspot regions in BRCA1 and BRCA2 where missense variation is tolerated. Reports BRCA1 exon 11 (codons 224-1366) as a coldspot with 0 pathogenic or likely pathogenic missense variants and 93.8% VUS. NM_007294.3:c.1568T>G was not individually mentioned, but the variant falls within this coldspot region.→ BP1 Does not name this variant
Source detail
Exon 11 in BRCA1 and exons 10 and 11 in BRCA2 were considered potential coldspots, consistent with literature describing the lack of pathogenic missense variants outside of known critical domains.
Location Table 1; Results, paragraph on BRCA1 coldspots
Other recorded publications
-
PMID 23918944 ↗Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.Phillips KA et al. · 2013Evaluates the association between adjuvant tamoxifen treatment and contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. Discusses BRCA1/2 at the gene level; NM_007294.3:c.1568T>G was not identified in this paper.Does not name this variant
-
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 consensus guidelines for sequence variant interpretation. Provides the generic framework for variant classification criteria. Does not discuss the specific variant NM_007294.3:c.1568T>G.Does not name this variant
-
PMID 37937776 ↗Actionable Genotypes and Their Association with Life Span in Iceland.Assesses actionable genotypes and their association with life span in Iceland using the ACMG secondary findings gene list. NM_007294.3:c.1568T>G was not identified in this paper.Does not name this variant
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PMID 23788249 ↗ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.Green RC et al. · 2013ACMG recommendations for reporting incidental findings in clinical exome and genome sequencing. Lists 56 genes recommended for secondary finding reporting, including BRCA1. NM_007294.3:c.1568T>G was not identified in this paper.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. · 2014USPSTF recommendation statement on risk assessment, genetic counseling, and genetic testing for BRCA-related cancer. NM_007294.3:c.1568T>G was not identified in this paper.Does not name this variant
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PMID 25085752 ↗Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes.Describes development and validation of a history weighting algorithm for reclassification of BRCA1 and BRCA2 VUS. The algorithm uses personal and family cancer history to assign pathogenic or benign calls. NM_007294.3:c.1568T>G was not individually discussed.Does not name this variant
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PMID 25356965 ↗ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing.ACMG policy statement updating recommendations for analysis and reporting of secondary findings in clinical genome-scale sequencing. NM_007294.3:c.1568T>G was not identified in this paper.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Presents Sherloc, a comprehensive refinement of the ACMG-AMP variant classification criteria. NM_007294.3:c.1568T>G was not identified in this paper.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
1 / 1,613,758 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
6 Uncertain significance · 1 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 ↗
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/?term=NM_007294.3%3Ac.1568T%3EG
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-41245980-A-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-43093963-A-C?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/17-43093963-A-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_007294.3%3Ac.1568…
- OncoKB ↗www.oncokb.org/gene/BRCA1/L523W
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA1+c.1568T%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= 6.19672e-07; MAF= 0.00006%, 1/1613758 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.47521e-07; MAF= 0.00008%, 1/1179912 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (6 clinical laboratories) and as Likely benign (1 clinical laboratory). (ClinVarID = 54295)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.613. BayesDel score = 0.322592.
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.