About BRCA1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA1 c.5432A>G, p.(Gln1811Arg)
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 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: 2
Benign evidence criteria: 0
Pathogenic criteria applied · 2
PS3Strong
PS3 · strong
ENIGMA BRCA1 VCEP Table 9 assigns PS3_Strong for NM_007294.3:c.5432A>G (p.Gln1811Arg) based on three calibrated functional studies (Findlay 2018 PMID:30209399; Petitalot 2019 PMID:30257991; Fernandes 2019 PMID:30765603), all reporting protein function similar to pathogenic control variants. In the ENIGMA Supplementary Table 4 (ST4) functional assay dataset, this variant shows complete functional impact (LOF, IARC class 5 — Pathogenic) with three independent supporting publications.
PM2Supporting
PM2 · supporting
This variant is absent from gnomAD v2.1 (non-cancer, exome only subset). In gnomAD v4.1, one allele is observed in 1,614,234 alleles (AF=6.19×10⁻⁷; 0.00006%), in the European (non-Finnish) population. This extremely low population frequency meets the ENIGMA PM2_Supporting threshold (absent from v2.1 and v3.1 non-cancer subsets). The single allele in v4.1 at near-zero frequency does not negate this criterion.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
ENIGMA BRCA1 Table 3 combining rules applied: one Strong criterion (PS3) plus one Supporting criterion (PM2) does not satisfy any Likely Pathogenic combination (requires 2 Strong, or 1 Strong + 2 Supporting, or 1 Strong + 1-2 Moderate). No benign criteria are met. Under the ENIGMA point-based scoring system, PS3_Strong (4 pts) + PM2_Supporting (1 pt) = 5 pts, which falls within the Uncertain Significance range (-1 to 5). The variant is classified as a Variant of Uncertain Significance (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
1 / 1,614,234 alleles
gnomAD v4.1: 1 / 1,614,234 alleles. Recorded AF 6.19489e-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
10 reported laboratory submissions
6 Likely pathogenic · 2 Uncertain significance · 1 Likely Pathogenic · 1 pathogenic.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
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 · 10 not met · 4 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
PS3_Strong is met: three independent calibrated functional studies (Findlay 2018, Petitalot 2019, Fernandes 2019) demonstrate that p.Gln1811Arg exhibits protein function comparable to pathogenic control variants (ENIGMA Table 9; functional impact complete, IARC class 5).
PM2_Supporting is met: the variant is absent from gnomAD v2.1 (non-cancer exomes) and observed at extremely low frequency in gnomAD v4.1 (1/1,614,234 alleles; AF=6.19×10⁻⁷).
PP3 and BP4 are not met: BayesDel no-AF score of 0.192 falls in the intermediate range between the BP4 threshold (≤0.15) and the PP3 threshold (≥0.28) for variants inside the BRCT clinically important domain.
PP4 and BP5 are not met: the clinical-history likelihood ratio (LR=0.993 from Li et al. 2020, N=3 probands) falls within the neutral zone, neither supporting pathogenicity nor benignity.
PVS1, PM5, and BP1 are not applicable: PVS1 is restricted to null variants; PM5_PTC is N/A for exon E21(22) per ENIGMA Table 4; BP1 requires location outside a clinically important functional domain (Gln1811 is within the BRCT domain).
Under ENIGMA Table 3 combining rules, the evidence profile of one Strong criterion (PS3) plus one Supporting criterion (PM2) is insufficient to classify as Likely Pathogenic (requires ≥2 Strong, or 1 Strong + ≥2 Supporting, or 1 Strong + 1–2 Moderate). The variant is classified as a Variant of Uncertain Significance (VUS).
No criteria match.
Met · 2
PS3 StrongENIGMA BRCA1 VCEP Table 9 assigns PS3_Strong for NM_007294.3:c.5432A>G (p.Gln1811Arg) based on three calibrated functional studies (Findlay 2018 PMID:30209399; Petitalot 2019 PMID:30257991; Fernandes 2019 PMID:30765603), all reporting protein function similar to pathogenic control variants. In the ENIGMA Supplementary Table 4 (ST4) functional assay dataset, this variant shows complete functional impact (LOF, IARC class 5 — Pathogenic) with three independent supporting publications. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 9: PS3_Strong assigned — three calibrated studies show protein function similar to pathogenic controls.
- ENIGMA ST4: Functional impact — complete (LOF)
- IARC class 5 (Pathogenic)
- supported by 3 publications (3P).
- Findlay 2018 (PMID:30209399): saturation genome editing of BRCA1 — LOF classification.
- Petitalot 2019 (PMID:30257991): functional assay — 3P classification.
- Fernandes 2019 (PMID:30765603): functional assay — Pathogenic classification.
Sources
vcep_specifications_table9_v1_2_2024_11_18vcep_supplementarytables_v1_2_2024_11_18
PM2 SupportingThis variant is absent from gnomAD v2.1 (non-cancer, exome only subset). In gnomAD v4.1, one allele is observed in 1,614,234 alleles (AF=6.19×10⁻⁷; 0.00006%), in the European (non-Finnish) population. This extremely low population frequency meets the ENIGMA PM2_Supporting threshold (absent from v2.1 and v3.1 non-cancer subsets). The single allele in v4.1 at near-zero frequency does not negate this criterion. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (non-cancer
- exome).
- gnomAD v4.1: 1/1
- 614
- 234 alleles (AF=6.19×10⁻⁷)
- highest in European (non-Finnish): 1/1
- 180
- 044 alleles (AF=8.47×10⁻⁷).
- Homozygotes = 0 in all populations.
Still missing
- gnomAD v3.1 (non-cancer) data not available in evidence brief
- v4.1 supersedes v3.1.
Sources
Not met · 10 · evaluated, threshold not reached
PS1 No same-amino-acid-change comparator variant at position Gln1811 has been independently classified as Pathogenic or Likely Pathogenic by the ENIGMA expert panel. Other missense changes at this residue (c.5431C>A p.Gln1811Lys; c.5432A>C p.Gln1811Pro; c.5432A>T p.Gln1811Leu) have PS3 functional evidence in ENIGMA Table 9 but lack finalized pathogenic classifications for PS1 application. Additionally, the variant has SpliceAI max delta of 0.00, confirming no splicing effect, which satisfies the PS1 mechanistic requirement had a comparator been available. Details ▾Hide ▴
Evidence considered
- Residue Gln1811 has multiple missense variants with functional data (PS3 met for c.5432A>C
- c.5431C>A
- c.5432A>T) but none carry a finalized Pathogenic classification to serve as a PS1 comparator.
Sources
vcep_specifications_table9_v1_2_2024_11_18
PP3 The variant lies within the BRCT clinically important functional domain (aa 1650–1857; Gln1811). Under ENIGMA PP3 rules, a missense variant inside a clinically important domain requires a BayesDel no-AF score ≥0.28 for predicted protein impact, or SpliceAI ≥0.2 for predicted splicing impact. The BayesDel score is 0.192 (below the 0.28 threshold) and SpliceAI max delta is 0.00 (below the 0.2 threshold). Neither criterion for PP3 is satisfied. Details ▾Hide ▴
Evidence considered
- Residue Gln1811 is within the BRCT domain (aa 1650–1857)
- a clinically important functional domain.
- BayesDel no-AF score: 0.192 (<0.28 threshold for PP3).
- SpliceAI max delta: 0.00 (<0.2 threshold for PP3 via splicing).
Sources
PP4 The clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058) for this variant is LR=0.993 (LOG(LR)=−0.007, N=3 probands). This falls within the neutral zone (>0.48 and <2.08), below the PP4_Supporting threshold of LR≥2.08. ENIGMA specifies PP4 is used ONLY to capture combined LR toward pathogenicity from multifactorial likelihood clinical data. Details ▾Hide ▴
Evidence considered
- Li et al. 2020 clinical-history LR = 0.993 (N=3 probands). Neutral zone
- not meeting PP4 or BP5 thresholds.
Sources
vcep_pmid_31853058_brca1_clinical_history_lrPMID:31853058 ↗
BA1 ENIGMA BA1 threshold requires a filter allele frequency (FAF) >0.001 (0.1%) in gnomAD v2.1 and/or v3.1 non-cancer, non-founder populations. The variant allele frequency in gnomAD v4.1 is 6.19×10⁻⁷ (0.00006%), far below the BA1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 AF = 6.19×10⁻⁷ (0.00006%)
- far below BA1 threshold of 0.001 (0.1%).
Sources
BS1 ENIGMA BS1_Strong requires FAF >0.0001 (0.01%); BS1_Supporting requires FAF >0.00002 (0.002%) and ≤0.0001 (0.01%). The gnomAD v4.1 allele frequency of 6.19×10⁻⁷ (0.00006%) falls below both thresholds. The variant is too rare to meet BS1 at any strength. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 AF = 6.19×10⁻⁷
- below BS1_Supporting threshold of 2×10⁻⁵.
Sources
BS3 ENIGMA Table 9 assigns PS3_Strong for this variant based on calibrated functional studies showing protein function similar to pathogenic controls. The functional evidence supports a damaging (pathogenic) effect. BS3 requires well-established functional studies showing no damaging effect; the available evidence uniformly points in the pathogenic direction. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 9 assigns PS3_Strong — functional data support damaging effect
- not benign.
Sources
vcep_specifications_table9_v1_2_2024_11_18
BP1 ENIGMA BP1_Strong applies to missense variants located outside a (potentially) clinically important functional domain AND no splicing predicted (SpliceAI ≤0.1). The variant p.Gln1811Arg resides at amino acid position 1811 within the BRCT repeat domain (aa 1650–1857), which is a designated clinically important functional domain in the ENIGMA specification. BP1 is therefore not applicable. Details ▾Hide ▴
Evidence considered
- Gln1811 is within the BRCT domain (aa 1650–1857)
- a clinically important functional domain per ENIGMA. BP1 requires location outside such domains.
Sources
BP4 The variant lies within the BRCT clinically important functional domain. ENIGMA BP4 requires BayesDel no-AF ≤0.15 AND SpliceAI ≤0.1 for missense variants inside a clinically important domain. SpliceAI max delta is 0.00 (≤0.1, met), but the BayesDel no-AF score is 0.192, which exceeds the 0.15 threshold. BP4 is therefore not satisfied. Details ▾Hide ▴
Evidence considered
- Inside BRCT clinically important domain.
- BayesDel no-AF: 0.192 (>0.15 threshold for BP4).
- SpliceAI max delta: 0.00 (≤0.1
- met for splicing component).
Sources
BP5 The clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058) for this variant is LR=0.993. The ENIGMA BP5_Supporting threshold is LR ≤0.48. The observed LR of 0.993 falls in the neutral zone and does not meet the BP5 threshold at any strength. Details ▾Hide ▴
Evidence considered
- Li et al. 2020 clinical-history LR = 0.993 (>0.48 BP5_Supporting threshold).
Sources
vcep_pmid_31853058_brca1_clinical_history_lrPMID:31853058 ↗
BP7 ENIGMA BP7_Strong (RNA) applies to missense variants located outside a clinically important functional domain with mRNA evidence of no splicing impact. The variant is inside the BRCT domain (aa 1650–1857), excluding BP7_Strong. BP7_Supporting is reserved for silent variants inside clinically important domains when BP4 is met; this variant is a missense substitution. No BP7 strength is applicable. Details ▾Hide ▴
Evidence considered
- Missense variant inside BRCT clinically important domain. BP7_Strong excluded
- BP7_Supporting only for silent variants.
Sources
Not assessed · 4 · no assessment recorded
PS4 No case-control study with odds ratio and p-value meeting ENIGMA PS4 thresholds (p≤0.05, OR≥4, lower CI excludes 2.0) has been identified for this variant. Details ▾Hide ▴
Still missing
- Case-control data not available for this specific variant.
PP1 No co-segregation data or quantitative Bayes score analysis has been identified for this variant. Details ▾Hide ▴
Still missing
- Co-segregation analysis data not available.
BS2 No data on observation of this variant in healthy adult individuals without features of Fanconi anemia were available for ENIGMA BS2 point-based assessment. Details ▾Hide ▴
Still missing
- No BS2 proband-level observational data available.
BS4 No lack-of-segregation data or quantitative Bayes score analysis has been identified for this variant. Details ▾Hide ▴
Still missing
- Segregation analysis data not available.
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_007294.3:c.5432A>G is a missense variant (p.Gln1811Arg), not a null variant (nonsense, frameshift, canonical ±1,2 splice site, initiation codon, or exon deletion). PVS1 is restricted to null variants under the ENIGMA BRCA1 VCEP specification v1.2.0. Details ▾Hide ▴
Evidence considered
- Missense substitution
- PVS1 only applies to null variants per ENIGMA specification.
Sources
PS2 VCEPPS2 is marked Not Applicable in the ENIGMA BRCA1 CSPEC framework. Details ▾Hide ▴
PM1 VCEPPM1 is marked Not Applicable in the ENIGMA BRCA1 CSPEC framework. Details ▾Hide ▴
PM5 N/AENIGMA Table 4 specifies PM5_N/A for BRCA1 exon E21(22) (NM_007294.3 exon 22, legacy numbering), which is the exon containing c.5432. PM5_PTC is excluded for this exon per the ENIGMA specification. Additionally, this is a missense variant, not a PTC, and pm5_candidates.json confirms no classic same-residue missense comparator approach is applicable. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 4: PM5_N/A for exon E21(22).
- Missense variant
- PM5_PTC N/A. No same-residue pathogenic missense comparator identified for classic PM5.
Sources
vcep_specifications_table4_v1_2_2024_11_18pm5_candidates
PM6 VCEPPM6 is marked Not Applicable in the ENIGMA BRCA1 CSPEC framework. Details ▾Hide ▴
PP2 VCEPPP2 is marked Not Applicable in the ENIGMA BRCA1 CSPEC framework. Details ▾Hide ▴
PP5 VCEPPP5 is marked Not Applicable in the ENIGMA BRCA1 CSPEC framework. Details ▾Hide ▴
BP2 VCEPBP2 is marked Not Applicable in the ENIGMA BRCA1 CSPEC framework. Details ▾Hide ▴
BP6 VCEPBP6 is marked Not Applicable in the ENIGMA BRCA1 CSPEC framework. Details ▾Hide ▴
PS5 N/APS5 is marked Not Applicable in the ENIGMA BRCA1 CSPEC framework. Details ▾Hide ▴
Identifiers
- Gene
- BRCA1
- Transcript
- NM_007294.3
- Coding (HGVS c.)
- NM_007294.3:c.5432A>G
- Protein (HGVS p.)
- NP_009225.1:p.(Gln1811Arg)
- GRCh38
- chr17:43047678 T>C
- GRCh37
- chr17:41199695 T>C
- ClinVar
- 867391, 55627, 55578
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
—
Transcript span
—
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 / 1,614,234 alleles
AF 6.19e-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 / 1,614,234 alleles · 0 hom
| European (non-Finnish)1 / 1,180,044 | 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= 6.19489e-07; MAF= 0.00006%, 1/1614234 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.47426e-07; MAF= 0.00008%, 1/1180044 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
- 0.709
- BayesDel
- 0.192
How the predictions were used
PP3 The variant lies within the BRCT clinically important functional domain (aa 1650–1857; Gln1811). Under ENIGMA PP3 rules, a missense variant inside a clinically important domain requires a BayesDel no-AF score ≥0.28 for predicted protein impact, or SpliceAI ≥0.2 for predicted splicing impact. The BayesDel score is 0.192 (below the 0.28 threshold) and SpliceAI max delta is 0.00 (below the 0.2 threshold). Neither criterion for PP3 is satisfied. Details ▾Hide ▴
Evidence considered
- Residue Gln1811 is within the BRCT domain (aa 1650–1857)
- a clinically important functional domain.
- BayesDel no-AF score: 0.192 (<0.28 threshold for PP3).
- SpliceAI max delta: 0.00 (<0.2 threshold for PP3 via splicing).
Sources
BP4 The variant lies within the BRCT clinically important functional domain. ENIGMA BP4 requires BayesDel no-AF ≤0.15 AND SpliceAI ≤0.1 for missense variants inside a clinically important domain. SpliceAI max delta is 0.00 (≤0.1, met), but the BayesDel no-AF score is 0.192, which exceeds the 0.15 threshold. BP4 is therefore not satisfied. Details ▾Hide ▴
Evidence considered
- Inside BRCT clinically important domain.
- BayesDel no-AF: 0.192 (>0.15 threshold for BP4).
- SpliceAI max delta: 0.00 (≤0.1
- met for splicing component).
Sources
BP7 ENIGMA BP7_Strong (RNA) applies to missense variants located outside a clinically important functional domain with mRNA evidence of no splicing impact. The variant is inside the BRCT domain (aa 1650–1857), excluding BP7_Strong. BP7_Supporting is reserved for silent variants inside clinically important domains when BP4 is met; this variant is a missense substitution. No BP7 strength is applicable. Details ▾Hide ▴
Evidence considered
- Missense variant inside BRCT clinically important domain. BP7_Strong excluded
- BP7_Supporting only for silent variants.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.709. BayesDel score = 0.192033.
7 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Recorded publications
-
PMID 15172985 ↗Structure-based assessment of missense mutations in human BRCA1: implications for breast and ovarian cancer predisposition.Mirkovic N et al. · 2004Q1811R predicted to be deleterious based on structural analysis. The substitution introduces a charge change (Gln→Arg) in the putative phosphopeptide-binding groove of the BRCT domain (residues 1811–1813 are part of the functional site). Classified as likely to abolish function.Names this variant
Quoted passage
Q1811R — Q — Charge change in putative binding site.
Table 2, line 636–639
-
PMID 20516115 ↗Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays.Lee MS et al. · 2010Q1811R listed among 117 BRCA1 BRCT missense variants analyzed by protease sensitivity, phosphopeptide-binding, and transcriptional activation assays. The variant appears in a supplementary variant listing without individual functional data reported in the accessible full-text.Names this variant
Quoted passage
Q1811R
Line 846 (supplementary variant listing)
-
PMID 10946236 ↗The BRCA1 C-terminal domain: structure and function.Huyton T et al. · 2000Q1811R catalogued in a review of missense mutations within the BRCA1 BRCT domains. Classified as a surface-exposed residue (β-strand) predicted to affect protein interaction rather than fold stability. Sequence conservation at the position was noted as variable.Names this variant
Quoted passage
Q1811R — E — S — PI — Variable
Table 1 (line 591–595)
-
PMID 12496477 ↗Mutations in the BRCT domain confer temperature sensitivity to BRCA1 in transcription activation.Carvalho MA et al. · 2002Q1811R identified as a loss-of-function mutant in a yeast-based transcriptional activation screen. The variant was present in clone LF2 alongside P1812S and A1843P, precluding isolation of its individual effect. The triple-mutant clone abolished transcription activation at both 30°C and 37°C.Names this variant
Quoted passage
Q1811R and A1843P, found together in LF2, are unclassified variants listed in the Breast Cancer Information Core database.
Table 2 (LF2 clone), Results paragraph describing LF mutants
-
PMID 14534301 ↗Detection of protein folding defects caused by BRCA1-BRCT truncation and missense mutations.Williams RS et al. · 2003This paper assessed protein folding defects of 25 BRCA1 BRCT missense variants using a protease sensitivity assay. NM_007294.3:c.5432A>G (p.Gln1811Arg) was not among the variants tested.Does not name this variant
-
PMID 15235020 ↗Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation.Abkevich V et al. · 2004Q1811R classified in a multiple-sequence-alignment-based analysis of BRCA1 missense variants. The residue is fully conserved across orthologs, and the substitution received an Align-GVGD score of 54, placing it in the intermediate range.Names this variant
Quoted passage
Q1811R — 54 — fully conserved
Supplementary table (line 1539–1541)
-
PMID 37733863 ↗Accurate proteome-wide missense variant effect prediction with AlphaMissense.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
1 / 1,614,234 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 Likely pathogenic · 2 Uncertain significance · 1 Likely Pathogenic · 1 pathogenic
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/55578/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-41199695-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-43047678-T-C?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/17-43047678-T-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_007294.3%3Ac.5432…
- OncoKB ↗www.oncokb.org/gene/BRCA1/Q1811R
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA1+c.5432A%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= 6.19489e-07; MAF= 0.00006%, 1/1614234 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.47426e-07; MAF= 0.00008%, 1/1180044 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 Likely pathogenic (6 clinical laboratories) and as Uncertain significance (2 clinical laboratories) and as Likely Pathogenic (1 clinical laboratory) and as pathogenic (1 clinical laboratory). (ClinVarID = 55578)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.709. BayesDel score = 0.192033.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
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.