About BRCA1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA1 c.507G>A, p.(Gln169=)
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: 0
Benign evidence criteria: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BP1Strong
BP1 · strong
ENIGMA BP1_Strong applies to silent substitutions outside a (potentially) clinically important functional domain with no predicted splicing impact (SpliceAI ≤0.1). c.507G>A is a silent variant (p.Gln169=). Residue 169 is outside all three BRCA1 clinically important functional domains (RING aa2-101, coiled-coil aa1391-1424, BRCT repeats aa1650-1857). SpliceAI max delta score is 0.01, well below the 0.1 threshold. All conditions for BP1_Strong are satisfied.
BP6Supporting
BP6 · supporting
Expert panel Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) classified as Likely benign.
Recorded classification: Likely benign
ENIGMA Table 3: 1 Strong (Benign) + 1 Supporting (Benign) = Likely Benign. Point score: -5 (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
28 / 1,613,772 alleles
gnomAD v4.1: 28 / 1,613,772 alleles. Recorded AF 1.73507e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.06056e-05; MAF= 0.00106%, 3/282870 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 8.01025e-05; MAF= 0.00801%, 2/24968 alleles, homozygotes = 0).
No listed criterion applied
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
7 reported laboratory submissions
4 Likely benign · 1 Likely Benign · 1 likely benign · 1 Benign.
Functional evidence
Statement recorded
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
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.
29 criteria with recorded statuses: 2 met · 6 not met · 8 not assessed · 13 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
c.507G>A is a silent (synonymous) substitution in BRCA1 exon 7 producing p.Gln169= (NP_009225.1:p.(Q169=)).
BP1_Strong is met: the variant is a silent substitution at residue 169, which is outside all three BRCA1 clinically important functional domains (RING aa2-101, coiled-coil aa1391-1424, BRCT repeats aa1650-1857), and SpliceAI predicts no splicing impact (max delta 0.01).
The variant is present at very low frequency in gnomAD population databases (v2.1: 3/282870 alleles; v4.1: 28/1613772 alleles) but does not meet BS1 or BA1 thresholds.
PVS1, PS1, PS5, PM5, and BP4 are not applicable due to the silent nature of the variant. PP3 is not met (SpliceAI 0.01 < 0.2). PM2 is not met (variant is present in gnomAD).
PS3, BS3, and BP7 remain not assessed pending verification of a reported minigene splicing assay (Fraile-Bethencourt et al. 2017) that found no splicing aberration. Confirmation of this finding would support BS3 and BP7.
PP4 and BP5 are not assessed because the variant is not represented in the Li et al. 2020 (PMID:31853058) clinical-history likelihood ratio table or the Parsons et al. 2019 multifactorial dataset.
ClinVar reports an ENIGMA expert panel classification of Likely benign (ClinVar ID 185706, review status: reviewed by expert panel). The ENIGMA classification likely incorporates the minigene splicing evidence and/or additional clinical data not captured in the available VCEP spreadsheets.
Under strict ENIGMA Table 3 combining rules, BP1_Strong alone is insufficient to reach Likely Benign without at least one additional supporting benign criterion of a different evidence type. The available data therefore place this variant between Likely Benign (per ENIGMA expert panel classification) and VUS (per strict criteria-based adjudication without verified BS3/BP7).
No criteria match.
Met · 2
BP1 StrongENIGMA BP1_Strong applies to silent substitutions outside a (potentially) clinically important functional domain with no predicted splicing impact (SpliceAI ≤0.1). c.507G>A is a silent variant (p.Gln169=). Residue 169 is outside all three BRCA1 clinically important functional domains (RING aa2-101, coiled-coil aa1391-1424, BRCT repeats aa1650-1857). SpliceAI max delta score is 0.01, well below the 0.1 threshold. All conditions for BP1_Strong are satisfied. Details ▾Hide ▴
Evidence considered
- Silent variant p.Gln169= at residue 169
- outside all BRCA1 functional domains (RING aa2-101
- coiled-coil aa1391-1424
- BRCT aa1650-1857). SpliceAI max delta 0.01 ≤ 0.1.
Sources
Not met · 6 · evaluated, threshold not reached
PS4 No case-control study demonstrating statistically significant enrichment of c.507G>A in affected individuals compared to controls was identified. The variant is present in gnomAD across multiple populations at low frequency, which is inconsistent with the expectation for a pathogenic BRCA1 variant detectable by PS4 enrichment analysis. Details ▾Hide ▴
Evidence considered
- No case-control data available. gnomAD presence in multiple populations is inconsistent with pathogenic enrichment.
Sources
PM2 ENIGMA PM2_Supporting requires the variant to be absent from gnomAD v2.1 (non-cancer, exome only) and gnomAD v3.1 (non-cancer) outbred populations. c.507G>A is present in gnomAD v2.1 (3/282870 alleles, AF=1.06e-05) and v4.1 (28/1613772 alleles, AF=1.74e-05), including observations in African/African American and European (non-Finnish) populations. The variant is not absent from controls. Details ▾Hide ▴
Evidence considered
- Present in gnomAD v2.1 (3/282870) and v4.1 (28/1613772)
- not absent from outbred populations.
Sources
PP3 ENIGMA PP3 applies to silent variants only when SpliceAI ≥0.2, indicating a predicted splicing impact. SpliceAI max delta for c.507G>A is 0.01, well below the 0.2 threshold. The variant is also outside clinically important functional domains (p.Gln169 is not within RING aa2-101, coiled-coil aa1391-1424, or BRCT aa1650-1857), so the BayesDel-based protein impact rule for missense variants in functional domains is not applicable. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta 0.01 (<0.2 threshold). Variant outside functional domains
- BayesDel-based PP3 rule not applicable.
Sources
BA1 ENIGMA BA1 requires filter allele frequency (FAF) above 0.1% (FAF > 0.001) in gnomAD v2.1 (non-cancer, exome only) and/or gnomAD v3.1 (non-cancer), non-founder populations. The gnomAD v4.1 grpmax FAF is 1.455e-05 (0.00145%), and the v2.1 overall AF is 1.06e-05 (0.00106%). Both are well below the 0.1% BA1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=1.06e-05
- v4.1 grpmax FAF=1.455e-05
- both << 0.001 BA1 threshold.
Sources
BS1 ENIGMA BS1_Strong requires FAF > 0.0001 (0.01%), and BS1_Supporting requires FAF > 0.00002 (0.002%) and ≤ 0.0001 in gnomAD non-cancer non-founder populations. The highest observed FAF is gnomAD v4.1 grpmax = 1.455e-05 (0.00145%), which falls below the BS1_Supporting threshold of 0.002%. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF=1.455e-05 (<0.00002 BS1_Supporting threshold).
Sources
BP4 ENIGMA BP4_Supporting for silent variants applies only when the variant is located inside a (potentially) clinically important functional domain and SpliceAI ≤0.1. c.507G>A is at residue 169, which lies outside the BRCA1 functional domains (RING aa2-101, coiled-coil aa1391-1424, BRCT aa1650-1857). The missense/in-frame rule also requires location inside a functional domain. The intronic rule does not apply to this exonic variant. None of the ENIGMA BP4 criteria are triggered. Details ▾Hide ▴
Evidence considered
- Silent variant outside functional domains
- BP4 silent-variant rule requires location inside a functional domain. Not applicable.
Sources
Not assessed · 8 · no assessment recorded
PS3 c.507G>A is not listed in ENIGMA Specifications Table 9 (calibrated functional assay results). Exploratory evidence recovery identified a report that Fraile-Bethencourt et al. 2017 tested this variant in a minigene splicing assay and observed no splicing aberration, but the full text could not be verified and the PMID attribution in the exploratory output was inconsistent with known publications. No validated functional evidence is available for PS3 adjudication. Details ▾Hide ▴
Evidence considered
- Variant absent from ENIGMA Table 9 curated functional assay results. Exploratory minigene assay finding could not be verified.
Still missing
- Verify whether Fraile-Bethencourt et al. 2017 (Human Mutation) minigene splicing assay included c.507G>A and whether the result constitutes calibrated BS3-level evidence per ENIGMA.
Sources
vcep_specifications_table9_v1_2_2024_11_18
PP1 No co-segregation data are available for c.507G>A. ENIGMA PP1 requires a quantitative co-segregation analysis with LR ≥2.08:1. The variant is not represented in the Parsons et al. 2019 (HUMU-40-1557-s001) multifactorial dataset, and no family-based segregation studies were identified. Details ▾Hide ▴
Evidence considered
- Variant not present in Parsons et al. 2019 multifactorial dataset
- no segregation studies available.
Still missing
- No family-based co-segregation data identified.
Sources
vcep_humu_40_1557_s001
PP4 c.507G>A is not listed in the Li et al. 2020 (PMID:31853058) BRCA1 clinical-history likelihood ratio table, nor in the Parsons et al. 2019 (HUMU-40-1557-s001) multifactorial dataset. No clinical-history LR is available to support PP4 application. Details ▾Hide ▴
Evidence considered
- Variant not found in Li et al. 2020 BRCA1 clinical-history LR table or Parsons et al. 2019 multifactorial dataset.
Still missing
- No clinical-history likelihood ratio available for this variant.
Sources
vcep_pmid_31853058_brca1_clinical_history_lrvcep_humu_40_1557_s00131853058
BS2 ENIGMA BS2 is applied in the absence of Fanconi Anemia phenotype features, using a points-based system per Specifications Table 8. No proband-level data regarding co-occurrence of c.507G>A in trans with another BRCA1 variant, or systematic evaluation of Fanconi Anemia features, were available. Details ▾Hide ▴
Evidence considered
- No proband-level data available for BS2 points-based assessment.
Still missing
- No data on co-occurrence in trans or Fanconi Anemia phenotype absence.
BS3 c.507G>A is not listed in ENIGMA Specifications Table 9, which assigns calibrated PS3/BS3 codes based on published functional assay results. Exploratory evidence recovery suggested that a minigene splicing assay (Fraile-Bethencourt et al. 2017) found no splicing aberration for this variant, which would support BS3. However, the full text of this paper could not be verified, the PMID attribution in the exploratory output was inconsistent with known publications, and the finding is not reflected in the authoritative ENIGMA Table 9. Formal BS3 adjudication requires confirmation of the functional evidence source. Details ▾Hide ▴
Evidence considered
- Variant absent from ENIGMA Table 9. Exploratory minigene finding could not be verified against full text.
Still missing
- Verify Fraile-Bethencourt et al. 2017 minigene splicing assay result for c.507G>A and confirm whether it meets ENIGMA BS3 calibration standards.
Sources
vcep_specifications_table9_v1_2_2024_11_18
BS4 No lack-of-segregation data are available for c.507G>A. ENIGMA BS4 requires a quantitative co-segregation analysis (LR ≤0.48:1). The variant is not represented in the Parsons et al. 2019 multifactorial dataset, and no family-based segregation studies were identified. Details ▾Hide ▴
Evidence considered
- Variant not present in Parsons et al. 2019 multifactorial dataset
- no segregation studies against pathogenicity.
Still missing
- No lack-of-segregation data identified.
Sources
vcep_humu_40_1557_s001
BP5 c.507G>A is not listed in the Li et al. 2020 (PMID:31853058) BRCA1 clinical-history likelihood ratio table, nor in the Parsons et al. 2019 (HUMU-40-1557-s001) multifactorial dataset. No clinical-history LR against pathogenicity is available to support BP5 application. Details ▾Hide ▴
Evidence considered
- Variant not found in Li et al. 2020 BRCA1 clinical-history LR table or Parsons et al. 2019 multifactorial dataset.
Still missing
- No clinical-history LR against pathogenicity available.
Sources
vcep_pmid_31853058_brca1_clinical_history_lrvcep_humu_40_1557_s00131853058
BP7 ENIGMA BP7_Strong (RNA) requires well-established mRNA assay evidence showing no damaging effect on splicing. BP7_Supporting applies to silent variants inside a functional domain if BP4 is met, which does not apply here (variant is outside functional domains). No verified mRNA splicing assay data are available for c.507G>A. The exploratory evidence recovery suggested a minigene assay found no splicing aberration, but the full text could not be verified and this finding is not reflected in ENIGMA Table 9 or ST3 (splicing references). Details ▾Hide ▴
Evidence considered
- No verified mRNA splicing assay data. Exploratory finding of no splicing aberration could not be verified against full text.
Still missing
- Verify minigene/mRNA splicing assay data for c.507G>A from Fraile-Bethencourt et al. 2017 or other sources.
Sources
cspec ↗vcep_supplementarytables_v1_2_2024_11_18
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is applicable only to null variants (nonsense, frameshift, canonical ±1,2 splice site, initiation codon, exon deletion). NM_007294.4:c.507G>A is a silent substitution (p.Gln169=) and does not create a premature termination codon or disrupt a canonical splice site. Details ▾Hide ▴
Evidence considered
- Silent variant NP_009225.1:p.(Gln169=)
- not a null variant.
Sources
pvs1_variant_assessment
PS1 N/APS1 requires a missense substitution or splicing variant with the same predicted impact as a previously classified (likely) pathogenic variant. c.507G>A is a silent variant (p.=) with SpliceAI max delta 0.01 (≤0.1), indicating no predicted splicing impact. No same-residue pathogenic comparator or splicing-impact match exists. Details ▾Hide ▴
Evidence considered
- Silent variant with no predicted splicing impact (SpliceAI max delta 0.01).
Sources
PS2 VCEPPS2 (de novo) is not applicable per ENIGMA BRCA1/BRCA2 Specification v1.2 (CSPEC applicability: Not Applicable). Details ▾Hide ▴
PM1 VCEPPM1 is listed as Not Applicable per ENIGMA BRCA1/BRCA2 Specification v1.2 (CSPEC applicability: Not Applicable). Details ▾Hide ▴
PM3 N/APM3 (in trans with a pathogenic variant in a recessive disorder) is skipped per case instructions. BRCA1 is an autosomal dominant cancer susceptibility gene. Details ▾Hide ▴
No further detail was recorded.
PM4 VCEPPM4 (protein length change due to in-frame deletion/insertion or stop-loss) does not apply to single-nucleotide substitutions. c.507G>A is a substitution variant. Details ▾Hide ▴
No further detail was recorded.
PM5 N/APM5 in ENIGMA BRCA1 is repurposed for PTC (protein termination codon) logic, applied to null variants where a different proven pathogenic PTC variant has been observed in the same exon. c.507G>A is a silent variant (p.Gln169=), not a PTC, and does not produce a termination codon. Details ▾Hide ▴
Evidence considered
- PM5_PTC logic does not apply to silent variants
- variant does not create a termination codon.
Sources
pm5_candidatescspec ↗
PM6 VCEPPM6 (de novo) is not applicable per ENIGMA BRCA1/BRCA2 Specification v1.2 (CSPEC applicability: Not Applicable). Details ▾Hide ▴
PP2 VCEPPP2 is listed as Not Applicable per ENIGMA BRCA1/BRCA2 Specification v1.2 (CSPEC applicability: Not Applicable). Details ▾Hide ▴
PP5 VCEPPP5 is listed as Not Applicable per ENIGMA BRCA1/BRCA2 Specification v1.2 (CSPEC applicability: Not Applicable). Details ▾Hide ▴
BP2 VCEPBP2 is listed as Not Applicable per ENIGMA BRCA1/BRCA2 Specification v1.2 (CSPEC applicability: Not Applicable). Details ▾Hide ▴
BP3 VCEPBP3 (in-frame deletions/insertions in repetitive regions) does not apply to single-nucleotide substitutions. c.507G>A is a substitution variant. Details ▾Hide ▴
No further detail was recorded.
PS5 N/APS5 requires a novel missense variant at a residue where a different pathogenic missense change has been established. c.507G>A is a silent variant (p.Gln169=), not a missense substitution. Details ▾Hide ▴
Evidence considered
- Silent variant
- not a missense change at an established pathogenic residue.
Identifiers
- Gene
- BRCA1
- Transcript
- NM_007294.4
- Coding (HGVS c.)
- NM_007294.4:c.507G>A
- Protein (HGVS p.)
- NP_009225.1:p.(Gln169=)
- GRCh38
- chr17:43099815 C>T
- GRCh37
- chr17:41251832 C>T
- ClinVar
- 3658262, 185706, 55743
Gene diagram
Every interpreted variant in BRCA1, mapped onto the exon structure of NM_007294.4. Select a row to find it on the plot.
BRCA1NM_007294.4
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
28 / 1,613,772 alleles
AF 1.74e-05 · 0 homozygotes · FAF 1.45e-05
gnomAD v2.1
3 / 282,870 alleles
AF 1.06e-05 · 0 homozygotes
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 1.7e-05 · 28 / 1,613,772 alleles · 0 hom · FAF 1.5e-05
| African/African American3 / 75,036 | 4e-05 |
| European (non-Finnish)25 / 1,179,678 | 2.1e-05 |
0 alternate alleles recorded in 8 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 1.1e-05 · 3 / 282,870 alleles · 0 hom
| African/African American2 / 24,968 | 8e-05 |
| European (non-Finnish)1 / 129,174 | 7.7e-06 |
0 alternate alleles recorded in 6 other groups: Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.73507e-05; MAF= 0.00174%, 28/1613772 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 3.99808e-05; MAF= 0.00400%, 3/75036 alleles, homozygotes = 0); grpmax FAF= 1.455e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.06056e-05; MAF= 0.00106%, 3/282870 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 8.01025e-05; MAF= 0.00801%, 2/24968 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.014
- BayesDel
- Not available
How the predictions were used
PP3 ENIGMA PP3 applies to silent variants only when SpliceAI ≥0.2, indicating a predicted splicing impact. SpliceAI max delta for c.507G>A is 0.01, well below the 0.2 threshold. The variant is also outside clinically important functional domains (p.Gln169 is not within RING aa2-101, coiled-coil aa1391-1424, or BRCT aa1650-1857), so the BayesDel-based protein impact rule for missense variants in functional domains is not applicable. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta 0.01 (<0.2 threshold). Variant outside functional domains
- BayesDel-based PP3 rule not applicable.
Sources
BP4 ENIGMA BP4_Supporting for silent variants applies only when the variant is located inside a (potentially) clinically important functional domain and SpliceAI ≤0.1. c.507G>A is at residue 169, which lies outside the BRCA1 functional domains (RING aa2-101, coiled-coil aa1391-1424, BRCT aa1650-1857). The missense/in-frame rule also requires location inside a functional domain. The intronic rule does not apply to this exonic variant. None of the ENIGMA BP4 criteria are triggered. Details ▾Hide ▴
Evidence considered
- Silent variant outside functional domains
- BP4 silent-variant rule requires location inside a functional domain. Not applicable.
Sources
BP7 ENIGMA BP7_Strong (RNA) requires well-established mRNA assay evidence showing no damaging effect on splicing. BP7_Supporting applies to silent variants inside a functional domain if BP4 is met, which does not apply here (variant is outside functional domains). No verified mRNA splicing assay data are available for c.507G>A. The exploratory evidence recovery suggested a minigene assay found no splicing aberration, but the full text could not be verified and this finding is not reflected in ENIGMA Table 9 or ST3 (splicing references). Details ▾Hide ▴
Evidence considered
- No verified mRNA splicing assay data. Exploratory finding of no splicing aberration could not be verified against full text.
Still missing
- Verify minigene/mRNA splicing assay data for c.507G>A from Fraile-Bethencourt et al. 2017 or other sources.
Sources
cspec ↗vcep_supplementarytables_v1_2_2024_11_18
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.014.
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 23918944 ↗Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.No 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 12692171 ↗American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility.American Society of Clinical Oncology · 2003No 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.Trepanier A et al. · 2004No paper-specific finding is recorded.
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PMID 17392385 ↗American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography.Saslow D et al. · 2007No paper-specific finding is recorded.
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PMID 17508274 ↗Risk assessment and genetic counseling for hereditary breast and ovarian cancer: recommendations of the National Society of Genetic Counselors.Berliner JL et al. · 2007No paper-specific finding is recorded.
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PMID 18163131 ↗The emerging landscape of breast cancer susceptibility.Stratton MR et al. · 2008No 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
28 / 1,613,772 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.010
Open source ↗
ClinVar
4 Likely benign · 1 Likely Benign · 1 likely benign · 1 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/variation/185706/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-41251832-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-43099815-C-T?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_007294.4%3Ac.507G…
- OncoKB ↗www.oncokb.org/gene/BRCA1/Q169=
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA1+c.507G%3EA
- 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= 1.73507e-05; MAF= 0.00174%, 28/1613772 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 3.99808e-05; MAF= 0.00400%, 3/75036 alleles, homozygotes = 0); grpmax FAF= 1.455e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.06056e-05; MAF= 0.00106%, 3/282870 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 8.01025e-05; MAF= 0.00801%, 2/24968 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Likely benign (4 clinical laboratories) and as Likely Benign (1 clinical laboratory) and as likely benign (1 clinical laboratory) and as Benign (1 clinical laboratory) and as Likely benign by Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) (expert panel). (ClinVarID = 185706)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.014.
Functional
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
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.