About BRCA1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA1 c.1233T>G, p.(Asp411Glu)
Classification
Not classified
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. Select a step to read what it means.
Not classified yet.Select a step to read what it means.
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
ENIGMA BS1_Strong applies when FAF exceeds 0.01% (FAF > 0.0001). gnomAD v2.1 grpmax FAF is 0.00024454 (0.024%); the variant is observed in 12/282,222 total alleles (AF=4.25e-05) with highest subpopulation frequency in the African/African American population (11/24,934 alleles, AF=0.044%). This exceeds the ENIGMA BS1_Strong threshold of >0.01%.
BS3Strong
BS3 · strong
ENIGMA Table 9 (v1.2.0) explicitly assigns BS3_Strong for NM_007294.3:c.1233T>G (p.Asp411Glu). One calibrated functional study (Bouwman et al. 2020, PMID:32546644) demonstrates that this variant exhibits protein function similar to benign control variants in homologous recombination repair complementation assays, meeting the criteria for well-established functional evidence of no damaging effect.
BP1Strong
BP1 · strong
ENIGMA BP1_Strong applies to missense variants located outside all (potentially) clinically important functional domains with no predicted splicing impact (SpliceAI ≤0.1). Codon 411 is outside the three defined domains: RING (aa 2-101), coiled-coil (aa 1391-1424), and BRCT (aa 1650-1857). SpliceAI max delta score is 0.07 (≤0.1). Both conditions for BP1_Strong are satisfied.
BP6Supporting
BP6 · supporting
Expert panel ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen classified as Benign.
Recorded classification: Not classified
No source classification-combination explanation was recorded.
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
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.25197e-05; MAF= 0.00425%, 12/282222 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000441165; MAF= 0.04412%, 11/24934 alleles, homozygotes = 0); grpmax FAF= 0.00024454.
SpliceAI score
0.070 maximum delta
Recorded SpliceAI maximum delta score: 0.070. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
11 reported laboratory submissions
5 Likely benign · 4 Benign · 2 Uncertain significance.
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.
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: 4 met · 10 not met · 2 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.1233T>G (p.Asp411Glu) is a missense variant in BRCA1 exon 10, classified as Benign by the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel (ClinVar Variation ID: 41804).
This variant is present in gnomAD v2.1 at 12/282,222 alleles (AF=4.25e-05) with a grpmax filter allele frequency of 0.024% (0.00024454) in the African/African American subpopulation (11/24,934 alleles), exceeding the ENIGMA BS1_Strong threshold of >0.01%.
ENIGMA Table 9 (v1.2.0) assigns BS3_Strong to this variant based on calibrated functional assay evidence from Bouwman et al. 2020 (PMID:32546644), demonstrating protein function in homologous recombination repair complementation similar to benign control variants.
Codon 411 is located outside all three (potentially) clinically important functional domains defined by ENIGMA for BRCA1: RING finger (aa 2-101), coiled-coil (aa 1391-1424), and BRCT repeats (aa 1650-1857). SpliceAI predicts no splicing impact (max delta score 0.07). These findings satisfy ENIGMA BP1_Strong criteria.
Parsons et al. 2019 multifactorial likelihood analysis (PMID:31131967) reports a combined LR of 1.29, a segregation LR of 1.93, and a family history LR of 6.48 for this variant. The combined LR is in the neutral range and does not independently support either pathogenic (PP4) or benign (BP5) classification.
No evidence was found to support any pathogenic criterion. PVS1, PS1, PS2, PS3, PS4, PS5, PM1, PM2, PM5, PM6, PP1, PP2, PP3, PP4, and PP5 are all either not met or not applicable.
Under the ENIGMA Table 3 combination rules, two or more Strong Benign criteria support a Benign classification. The three Strong Benign criteria met (BS1_Strong, BS3_Strong, BP1_Strong) satisfy the Benign classification threshold.
No criteria match.
Met · 4
BS1 StrongENIGMA BS1_Strong applies when FAF exceeds 0.01% (FAF > 0.0001). gnomAD v2.1 grpmax FAF is 0.00024454 (0.024%); the variant is observed in 12/282,222 total alleles (AF=4.25e-05) with highest subpopulation frequency in the African/African American population (11/24,934 alleles, AF=0.044%). This exceeds the ENIGMA BS1_Strong threshold of >0.01%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: grpmax FAF=0.00024454 (0.024%) > ENIGMA BS1_Strong threshold of 0.01%. 12 total alleles
- 11 in AFR subpopulation.
Sources
BS3 StrongENIGMA Table 9 (v1.2.0) explicitly assigns BS3_Strong for NM_007294.3:c.1233T>G (p.Asp411Glu). One calibrated functional study (Bouwman et al. 2020, PMID:32546644) demonstrates that this variant exhibits protein function similar to benign control variants in homologous recombination repair complementation assays, meeting the criteria for well-established functional evidence of no damaging effect. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 9: BS3_Strong assigned
- Bouwman 2020 functional assay shows no damaging effect on protein function in HR complementation.
Sources
vcep_specifications_table9_v1_2_2024_11_1832546644
BP1 StrongENIGMA BP1_Strong applies to missense variants located outside all (potentially) clinically important functional domains with no predicted splicing impact (SpliceAI ≤0.1). Codon 411 is outside the three defined domains: RING (aa 2-101), coiled-coil (aa 1391-1424), and BRCT (aa 1650-1857). SpliceAI max delta score is 0.07 (≤0.1). Both conditions for BP1_Strong are satisfied. Details ▾Hide ▴
Evidence considered
- Position 411 outside all three clinically important functional domains (RING 2-101
- coiled-coil 1391-1424
- BRCT 1650-1857)
- SpliceAI max delta=0.07 (≤0.1).
Sources
Not met · 10 · evaluated, threshold not reached
PS1 No previously classified pathogenic or likely pathogenic missense variant at codon 411 with the same amino acid change (p.Asp411Glu) was identified. No known pathogenic variant at this residue with the same predicted protein effect. Details ▾Hide ▴
Evidence considered
- No established pathogenic variant with the same amino acid change at codon 411.
PS3 ENIGMA Table 9 (v1.2.0) assigns BS3_Strong for this variant, not PS3. Functional evidence from calibrated assays (Bouwman 2020, PMID:32546644) demonstrates protein function similar to benign control variants, supporting a benign interpretation rather than a damaging effect. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 9: c.1233T>G assigned BS3_Strong
- Bouwman 2020 functional assay shows no damaging effect on protein function.
Sources
vcep_specifications_table9_v1_2_2024_11_1832546644
PS4 No case-control study has demonstrated significantly increased prevalence of this variant in affected individuals (p≤0.05, OR≥4). The variant is observed in gnomAD population controls (12/282,222 alleles), inconsistent with pathogenic enrichment. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 12 alleles in 282
- 222 population controls
- no case-control enrichment data.
Sources
PM2 ENIGMA PM2_Supporting requires absence from gnomAD v2.1 (non-cancer, exome only subset) and gnomAD v3.1 (non-cancer). This variant is present in gnomAD v2.1 at 12/282,222 alleles (AF=4.25e-05) with grpmax FAF=0.00024454, and is absent from gnomAD v4.1. The presence in gnomAD v2.1 precludes application of PM2_Supporting. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 12/282
- 222 alleles (AF=4.25e-05)
- grpmax FAF=0.00024454
- gnomAD v4.1: absent.
Sources
PP3 ENIGMA PP3 requires either (a) missense variant inside a clinically important functional domain with BayesDel no-AF score ≥0.28, or (b) SpliceAI delta score ≥0.2. Position 411 is outside all three clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857). SpliceAI max delta score is 0.07 (<0.2). Neither condition is met. Details ▾Hide ▴
Evidence considered
- Position 411 outside functional domains
- BayesDel=-0.196 (not ≥0.28)
- SpliceAI max delta=0.07 (not ≥0.2).
Sources
PP4 ENIGMA PP4 uses multifactorial combined likelihood ratio toward pathogenicity. Parsons et al. 2019 (PMID:31131967) reports a combined LR of 1.29 for this variant, which falls below the PP4_Supporting threshold of ≥2.08. The variant is not listed in the Li et al. 2020 clinical-history LR table (PMID:31853058). The combined multifactorial evidence is neutral. Details ▾Hide ▴
Evidence considered
- Parsons 2019 SuppT1: Combined LR=1.29 (neutral
- below PP4_Supporting ≥2.08)
- not in Li 2020 clinical-history LR table.
Sources
vcep_humu_40_1557_s001vcep_pmid_31853058_brca1_clinical_history_lr
BA1 ENIGMA BA1 requires filter allele frequency (FAF) above 0.1% (FAF > 0.001) in gnomAD v2.1 (non-cancer, exome only subset) and/or gnomAD v3.1 (non-cancer). gnomAD v2.1 grpmax FAF is 0.00024454 (0.024%), below the 0.1% threshold. The variant is absent from gnomAD v4.1. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 grpmax FAF=0.00024454 (0.024%)
- below BA1 threshold of >0.1% (0.001).
Sources
BS4 ENIGMA BS4 requires a segregation LR ≤0.48 (Supporting) or lower for stronger evidence levels. Parsons et al. 2019 (PMID:31131967) reports a segregation LR of 1.93 for this variant, which does not meet even the BS4_Supporting threshold of ≤0.48. The available segregation data does not support lack of segregation with disease. Details ▾Hide ▴
Evidence considered
- Parsons 2019 SuppT1: Segregation LR=1.93
- above BS4_Supporting threshold of ≤0.48.
Sources
vcep_humu_40_1557_s001
BP5 ENIGMA BP5 uses multifactorial combined likelihood ratio against pathogenicity. Parsons et al. 2019 (PMID:31131967) reports a combined LR of 1.29 for this variant, which is above the BP5_Supporting threshold of ≤0.48. The variant is not listed in the Li et al. 2020 clinical-history LR table (PMID:31853058). The combined multifactorial evidence does not support a benign interpretation via BP5. Details ▾Hide ▴
Evidence considered
- Parsons 2019 SuppT1: Combined LR=1.29 (above BP5_Supporting threshold of ≤0.48)
- not in Li 2020 clinical-history LR table.
Sources
vcep_humu_40_1557_s001vcep_pmid_31853058_brca1_clinical_history_lr
BP7 ENIGMA BP7_Strong(RNA) requires well-established mRNA transcript assay evidence showing no damaging effect on splicing for missense variants outside clinically important functional domains. No variant-specific mRNA splicing assay data was identified for NM_007294.3:c.1233T>G. SpliceAI predicts no splicing impact (max delta=0.07) but computational prediction alone does not satisfy the ENIGMA requirement for BP7(RNA). ENIGMA BP7_Supporting applies only to silent variants inside domains and is not applicable here. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta=0.07 predicts no splicing impact
- but no variant-specific mRNA assay data available to satisfy BP7_Strong(RNA) requirements.
Still missing
- No variant-specific mRNA transcript assay data identified.
Sources
Not assessed · 2 · no assessment recorded
PP1 No co-segregation data demonstrating segregation of this variant with disease in multiple affected family members was identified. Parsons et al. 2019 (PMID:31131967) reports a segregation LR of 1.93 for this variant, which is in the neutral range (LR <2.08) and does not support co-segregation with disease. Details ▾Hide ▴
Evidence considered
- Parsons 2019 SuppT1: Segregation LR=1.93 (neutral
- does not support co-segregation).
Still missing
- No published pedigree or co-segregation analysis identified for this variant.
Sources
vcep_humu_40_1557_s001
BS2 ENIGMA BS2 requires proband-level data demonstrating observation in a healthy adult in the absence of Fanconi Anemia phenotype. No such proband data was available for this variant. Details ▾Hide ▴
Evidence considered
- No BS2 points-assessable proband data identified.
Still missing
- No proband-level data for BS2 point assignment per ENIGMA Table 8.
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable to missense variants. NM_007294.3:c.1233T>G (p.Asp411Glu) is a missense substitution, not a null variant (nonsense, frameshift, or canonical splice site). Details ▾Hide ▴
Evidence considered
- Missense variant — not a null variant eligible for PVS1.
PS2 VCEPENIGMA BRCA1/BRCA2 VCEP v1.2.0 rules this criterion not applicable. Details ▾Hide ▴
PM1 VCEPENIGMA BRCA1/BRCA2 VCEP v1.2.0 rules PM1 not applicable. Additionally, position 411 is outside the three (potentially) clinically important functional domains defined by ENIGMA: RING (aa 2-101), coiled-coil (aa 1391-1424), and BRCT (aa 1650-1857). Details ▾Hide ▴
Evidence considered
- ENIGMA VCEP explicitly marks PM1 as not applicable
- codon 411 is outside known functional domains.
Sources
PM5 N/AENIGMA repurposes PM5 exclusively for PTC (protein termination codon) variants, not for classic same-residue missense comparisons. NM_007294.3:c.1233T>G is a missense variant (p.Asp411Glu) and is not a PTC. Details ▾Hide ▴
Evidence considered
- ENIGMA PM5 applies only to PTC variants
- this missense variant is not eligible.
Sources
cspec ↗vcep_specifications_table4_v1_2_2024_11_18
PM6 VCEPENIGMA BRCA1/BRCA2 VCEP v1.2.0 rules this criterion not applicable. Details ▾Hide ▴
PP2 VCEPENIGMA BRCA1/BRCA2 VCEP v1.2.0 rules this criterion not applicable. Details ▾Hide ▴
PP5 VCEPENIGMA BRCA1/BRCA2 VCEP v1.2.0 rules this criterion not applicable. Details ▾Hide ▴
BP2 VCEPENIGMA BRCA1/BRCA2 VCEP v1.2.0 rules this criterion not applicable. Details ▾Hide ▴
BP4 N/AENIGMA BP4_Supporting applies exclusively to missense variants located inside a (potentially) clinically important functional domain with BayesDel no-AF score ≤0.15 and SpliceAI ≤0.1. Codon 411 is outside all three defined domains. While BayesDel (-0.196) and SpliceAI (0.07) would satisfy the computational thresholds, the domain location requirement is not met, so BP4 does not apply under ENIGMA rules. Details ▾Hide ▴
Evidence considered
- ENIGMA BP4 requires variant inside functional domain
- codon 411 is outside. BayesDel=-0.196
- SpliceAI=0.07.
Sources
PS5 N/AENIGMA BRCA1/BRCA2 VCEP v1.2.0 rules PP5 not applicable; PS5 is similarly excluded from the ENIGMA framework as a source-based criterion redundant with expert panel review. Details ▾Hide ▴
Evidence considered
- ENIGMA VCEP excludes PP5/PS5 as not applicable for BRCA1/BRCA2 variant classification.
Sources
Identifiers
- Gene
- BRCA1
- Transcript
- NM_007294.3
- Coding (HGVS c.)
- NM_007294.3:c.1233T>G
- Protein (HGVS p.)
- NP_009225.1:p.(Asp411Glu)
- GRCh38
- chr17:43094298 A>C
- GRCh37
- chr17:41246315 A>C
- ClinVar
- 2450665, 1803468, 1774022, 1330070, 658642, 628257, 229934, 229900, 184733, 41804
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
Allele count data not recorded
gnomAD v2.1
12 / 282,222 alleles
AF 4.25e-05 · 0 homozygotes · FAF 0.000245
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v2.1
AF 4.3e-05 · 12 / 282,222 alleles · 0 hom · FAF 0.00024
| African/African American11 / 24,934 | 0.00044 |
| Admixed American1 / 35,410 | 2.8e-05 |
0 alternate alleles recorded in 6 other groups: Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.25197e-05; MAF= 0.00425%, 12/282222 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000441165; MAF= 0.04412%, 11/24934 alleles, homozygotes = 0); grpmax FAF= 0.00024454.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.639
- BayesDel
- -0.196
How the predictions were used
PP3 ENIGMA PP3 requires either (a) missense variant inside a clinically important functional domain with BayesDel no-AF score ≥0.28, or (b) SpliceAI delta score ≥0.2. Position 411 is outside all three clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857). SpliceAI max delta score is 0.07 (<0.2). Neither condition is met. Details ▾Hide ▴
Evidence considered
- Position 411 outside functional domains
- BayesDel=-0.196 (not ≥0.28)
- SpliceAI max delta=0.07 (not ≥0.2).
Sources
BP7 ENIGMA BP7_Strong(RNA) requires well-established mRNA transcript assay evidence showing no damaging effect on splicing for missense variants outside clinically important functional domains. No variant-specific mRNA splicing assay data was identified for NM_007294.3:c.1233T>G. SpliceAI predicts no splicing impact (max delta=0.07) but computational prediction alone does not satisfy the ENIGMA requirement for BP7(RNA). ENIGMA BP7_Supporting applies only to silent variants inside domains and is not applicable here. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta=0.07 predicts no splicing impact
- but no variant-specific mRNA assay data available to satisfy BP7_Strong(RNA) requirements.
Still missing
- No variant-specific mRNA transcript assay data identified.
Sources
BP4 N/AENIGMA BP4_Supporting applies exclusively to missense variants located inside a (potentially) clinically important functional domain with BayesDel no-AF score ≤0.15 and SpliceAI ≤0.1. Codon 411 is outside all three defined domains. While BayesDel (-0.196) and SpliceAI (0.07) would satisfy the computational thresholds, the domain location requirement is not met, so BP4 does not apply under ENIGMA rules. Details ▾Hide ▴
Evidence considered
- ENIGMA BP4 requires variant inside functional domain
- codon 411 is outside. BayesDel=-0.196
- SpliceAI=0.07.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.07). REVEL score = 0.639. BayesDel score = -0.196447.
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 15235020 ↗Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation.Abkevich V et al. · 2004No paper-specific finding is recorded.
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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.
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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.
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PMID 16518693 ↗Natural selection and mammalian BRCA1 sequences: elucidating functionally important sites relevant to breast cancer susceptibility in humans.Burk-Herrick A et al. · 2006No paper-specific finding is recorded.
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PMID 21523855 ↗Comprehensive prediction of mRNA splicing effects of BRCA1 and BRCA2 variants.Mucaki EJ et al. · 2011No paper-specific finding is recorded.
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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.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.
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PMID 28283652 ↗BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer.Shimelis H et al. · 2017No paper-specific finding is recorded.
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
Captured gnomAD v4.1 source record
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.070
Open source ↗
ClinVar
5 Likely benign · 4 Benign · 2 Uncertain significance
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1530970787
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/41804/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-41246315-A-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-43094298-A-C?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_007294.3%3Ac.1233…
- OncoKB ↗www.oncokb.org/gene/BRCA1/D411E
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA1+c.1233T%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
Absent from gnomAD v4.1.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.25197e-05; MAF= 0.00425%, 12/282222 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000441165; MAF= 0.04412%, 11/24934 alleles, homozygotes = 0); grpmax FAF= 0.00024454.
ClinVar
This variant has been reported in ClinVar as Likely benign (5 clinical laboratories) and as Benign (4 clinical laboratories) and as Uncertain significance (2 clinical laboratories) and as Benign by ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 41804)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.07). REVEL score = 0.639. BayesDel score = -0.196447.
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.