About BRCA1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA1 c.2347A>G, p.(Ile783Val)
Classification
Benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen BRCA1 VCEP v1.2. 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: 3
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 3
BS1Strong
BS1 · strong
ENIGMA BS1_Strong: filter allele frequency (FAF) >0.01% (0.0001) in gnomAD non-cancer, non-founder populations. This variant has grpmax FAF = 0.0632% (0.000632) in gnomAD v2.1 East Asian population (18/18,394 alleles, AF=0.098%) and grpmax FAF = 0.0223% (0.000223) in gnomAD v4.1. Both exceed the BS1_Strong threshold. The East Asian population is not a founder population under ENIGMA criteria.
BS3Strong
BS3 · strong
ENIGMA Specifications Table 9 assigns BS3_Strong to NM_007294.4:c.2347A>G (p.Ile783Val). A calibrated functional study (Bouwman 2020, PMID:32546644) demonstrated that this variant exhibits protein function similar to benign control variants in a homologous recombination repair complementation assay, indicating no damaging effect on protein function.
BP1Strong
BP1 · strong
ENIGMA BP1_Strong applies to missense variants located outside a (potentially) clinically important functional domain AND with no predicted splicing impact (SpliceAI ≤0.1). p.Ile783Val is a missense variant at amino acid position 783, which is outside all three ENIGMA-defined clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857). SpliceAI max delta score is 0.0, confirming no predicted splicing impact.
Recorded classification: Benign
ENIGMA BRCA1 v1.2 Table 3 combination rules. Three strong benign criteria met (BS1_Strong, BS3_Strong, BP1_Strong), satisfying the rule: ≥2 Strong (Benign) criteria → Benign. No pathogenic criteria are met, so the ENIGMA conflicting-evidence point system is not invoked.
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
18 / 1,613,836 alleles
gnomAD v4.1: 18 / 1,613,836 alleles. Recorded AF 1.11535e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.17881e-05; MAF= 0.00718%, 18/250738 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.00097858; MAF= 0.09786%, 18/18394 alleles, homozygotes = 0); grpmax FAF= 0.00063201.
gnomAD-Canada
Not available in 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
11 reported laboratory submissions
5 Benign · 3 Likely benign · 2 Uncertain significance · 1 benign. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
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.
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, with the data and sources behind each one.
29 criteria with recorded statuses: 3 met · 6 not met · 7 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
NM_007294.4:c.2347A>G (p.Ile783Val) is observed in gnomAD at a filter allele frequency of 0.0632% (18/250,738 alleles in v2.1, grpmax FAF in East Asian population), exceeding the ENIGMA BS1_Strong threshold of 0.01%.
A calibrated functional study (Bouwman et al. 2020, PMID:32546644) demonstrated that p.Ile783Val exhibits protein function similar to benign control variants in a homologous recombination repair complementation assay. ENIGMA Specifications Table 9 assigns BS3_Strong to this variant.
The variant is a missense substitution at amino acid 783, located outside all ENIGMA-defined clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857), with no predicted splicing impact (SpliceAI max delta=0.0), satisfying ENIGMA BP1_Strong.
Three strong benign criteria (BS1, BS3, BP1) are met, satisfying ENIGMA Table 3 rule for Benign classification (≥2 Strong Benign criteria).
No criteria match.
Met · 3
BS1 StrongENIGMA BS1_Strong: filter allele frequency (FAF) >0.01% (0.0001) in gnomAD non-cancer, non-founder populations. This variant has grpmax FAF = 0.0632% (0.000632) in gnomAD v2.1 East Asian population (18/18,394 alleles, AF=0.098%) and grpmax FAF = 0.0223% (0.000223) in gnomAD v4.1. Both exceed the BS1_Strong threshold. The East Asian population is not a founder population under ENIGMA criteria. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 grpmax FAF=0.0632% > 0.01% threshold (East Asian subpopulation)
- gnomAD v4.1 grpmax FAF=0.0223% > 0.01% threshold
- Variant observed at highest frequency in East Asian population (v2.1 AF=0.098%
- 18/18
- 394 alleles)
Sources
BS3 StrongENIGMA Specifications Table 9 assigns BS3_Strong to NM_007294.4:c.2347A>G (p.Ile783Val). A calibrated functional study (Bouwman 2020, PMID:32546644) demonstrated that this variant exhibits protein function similar to benign control variants in a homologous recombination repair complementation assay, indicating no damaging effect on protein function. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 9 assigns BS3_Strong based on Bouwman 2020 (PMID:32546644)
- Homologous recombination repair complementation assay showed (likely) neutral functional effect
Sources
vcep_specifications_table9_v1_2_2024_11_18
BP1 StrongENIGMA BP1_Strong applies to missense variants located outside a (potentially) clinically important functional domain AND with no predicted splicing impact (SpliceAI ≤0.1). p.Ile783Val is a missense variant at amino acid position 783, which is outside all three ENIGMA-defined clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857). SpliceAI max delta score is 0.0, confirming no predicted splicing impact. Details ▾Hide ▴
Evidence considered
- Missense variant at position 783 — outside RING (2-101)
- coiled-coil (1391-1424)
- and BRCT (1650-1857) domains
- SpliceAI max delta = 0.0 — no predicted splicing impact
Sources
Not met · 6 · evaluated, threshold not reached
PS3 ENIGMA Specifications Table 9 assigns BS3_Strong to c.2347A>G (p.Ile783Val), indicating calibrated functional studies demonstrate protein function similar to benign control variants (Bouwman 2020, PMID:32546644). No evidence of damaging effect on protein function was identified. Functional evidence supports benign, not pathogenic, impact for this variant. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 9 assigns BS3_Strong based on Bouwman 2020 (PMID:32546644) showing (likely) neutral functional effect in homologous recombination repair complementation assay.
Sources
vcep_specifications_table9_v1_2_2024_11_18
PM2 ENIGMA PM2_Supporting requires absence from controls in gnomAD v2.1 (non-cancer, exome) and gnomAD v3.1 (non-cancer). This variant is present in gnomAD v2.1 with 18/250,738 alleles (AF=0.0072%) and in gnomAD v4.1 with 18/1,613,836 alleles (AF=0.0011%). It is not absent from population databases. Details ▾Hide ▴
Evidence considered
- Present in gnomAD: v2.1 18/250
- 738 alleles (0.0072%)
- v4.1 18/1
- 613
- 836 alleles (0.0011%). Does not meet absence-from-controls requirement for PM2.
Sources
PP3 ENIGMA PP3 applies to missense variants inside a clinically important functional domain with BayesDel ≥0.28, or when SpliceAI ≥0.2. Position 783 is outside all three ENIGMA domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857). BayesDel score is -0.316 (below 0.28 threshold). SpliceAI max delta is 0.0 (below 0.2 threshold). Neither criterion is satisfied. Details ▾Hide ▴
Evidence considered
- Position 783 outside functional domains
- BayesDel=-0.316 (<0.28)
- SpliceAI=0.0 (<0.2). No predicted pathogenic impact.
Sources
spliceai ↗bayesdel
BA1 ENIGMA BA1 requires filter allele frequency (FAF) >0.1% (0.001) in gnomAD v2.1 non-cancer exome and/or gnomAD v3.1 non-cancer, non-founder populations. gnomAD v2.1 grpmax FAF = 0.0632% (0.000632) and v4.1 grpmax FAF = 0.0223% (0.000223). Neither exceeds the 0.1% stand-alone benign threshold. Details ▾Hide ▴
Evidence considered
- grpmax FAF v2.1=0.0632% (<0.1%)
- v4.1=0.0223% (<0.1%). Does not meet BA1 stand-alone threshold.
Sources
BP4 ENIGMA BP4 applies to missense variants inside a clinically important functional domain with no predicted impact via protein change or splicing (BayesDel ≤0.15 AND SpliceAI ≤0.1). Position 783 is outside all three ENIGMA domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857). BP4 does not apply to variants outside these domains under ENIGMA rules; domain-external missense variants are captured by BP1 instead. Details ▾Hide ▴
Evidence considered
- Position 783 outside ENIGMA functional domains
- BP4 prerequisite (inside domain) not satisfied.
Sources
BP7 ENIGMA BP7_Strong (RNA) requires well-established functional studies showing no damaging effect on mRNA transcript profile (mRNA assay only). BS3_Strong is applied for protein-level functional neutrality; BP7 requires separate mRNA-level evidence. No mRNA-specific splicing or transcript assay data is available for this variant. SpliceAI predicts no splicing impact (max delta=0.0), but BP7 under ENIGMA requires experimental mRNA data, not predictions alone. BP7_Supporting applies only to silent or intronic variants, not missense substitutions. Details ▾Hide ▴
Evidence considered
- No mRNA-specific functional assay data available
- SpliceAI=0.0 is predictive but BP7 requires experimental mRNA evidence. BS3 already captures protein-level functional data.
Still missing
- mRNA transcript analysis could provide independent BP7 evidence if performed.
Sources
Not assessed · 7 · no assessment recorded
PS1 No previously classified pathogenic or likely pathogenic missense variant at the same residue (Ile783) was identified in available data. ENIGMA PS1 requires a same-residue comparator variant classified as pathogenic/likely pathogenic with no predicted splicing impact (SpliceAI ≤0.1). The pm5_candidates search found no eligible comparators under ENIGMA rules (PM5 repurposed for PTC variants only). Details ▾Hide ▴
Evidence considered
- No same-residue pathogenic missense comparator identified.
Still missing
- Manual literature review for Ile783 pathogenic substitutions may identify a comparator not captured in automated search.
Sources
pm5_candidates
PS4 No case-control data available for this variant. ENIGMA PS4 requires case-control study with p-value ≤0.05 and OR ≥4 (lower CI excludes 2.0). The variant is observed in gnomAD at low frequency (East Asian AF=0.098% in v2.1), but no formal case-control comparison meeting ENIGMA thresholds was identified. Details ▾Hide ▴
Evidence considered
- Variant present in population databases
- no case-control study data available.
Still missing
- Case-control data from East Asian breast/ovarian cancer cohorts could be informative given the variant's population distribution.
Sources
PP1 No co-segregation data available for this variant. ENIGMA PP1 requires quantitative co-segregation analysis with LR thresholds (Supporting ≥2.08, Moderate ≥4.3, Strong ≥18.7, Very Strong ≥350). No segregation analysis was identified in available data. Details ▾Hide ▴
Evidence considered
- No co-segregation data available.
Still missing
- Family segregation data would be informative but is not available in current case materials.
PP4 Variant c.2347A>G was not found in the ENIGMA clinical history likelihood ratio table (Li et al. 2020, PMID:31853058, BRCA1_clinical_history_LR.xlsx). No clinical-history LR is available for PP4 adjudication under ENIGMA rules. Details ▾Hide ▴
Evidence considered
- Variant absent from Li et al. 2020 clinical history LR table
- no LR value available.
Still missing
- Variant-specific clinical history data could be informative if available from alternative sources.
Sources
vcep_pmid_31853058_brca1_clinical_history_lr
BS2 ENIGMA BS2 requires proband-level data evaluated per Specifications Table 8, applied in the absence of Fanconi Anemia phenotype features. No proband-specific phenotype data is available in the current case materials to adjudicate BS2. Details ▾Hide ▴
Evidence considered
- Insufficient proband-level phenotype data for BS2 adjudication under ENIGMA Table 8.
Still missing
- Proband clinical phenotype data required for BS2 evaluation.
BS4 ENIGMA BS4 requires quantitative co-segregation analysis showing lack of segregation (LR thresholds). No segregation data is available for this variant in current case materials. Details ▾Hide ▴
Evidence considered
- No segregation data available.
Still missing
- Family segregation data could inform BS4 but is not available.
BP5 Variant c.2347A>G was not found in the ENIGMA clinical history likelihood ratio table (Li et al. 2020, PMID:31853058, BRCA1_clinical_history_LR.xlsx). No clinical-history LR against pathogenicity is available for BP5 adjudication under ENIGMA rules. Details ▾Hide ▴
Evidence considered
- Variant absent from Li et al. 2020 clinical history LR table
- no LR value available for BP5.
Sources
vcep_pmid_31853058_brca1_clinical_history_lr
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 applies only to null variants (nonsense, frameshift, canonical ±1,2 splice site, initiation codon, single/multi-exon deletion) per ENIGMA BRCA1 specification v1.2. NM_007294.4:c.2347A>G is a missense variant (p.Ile783Val) and does not qualify for PVS1. Details ▾Hide ▴
Evidence considered
- Missense substitution
- does not meet null-variant criteria for PVS1 under ENIGMA specification.
Sources
PS2 VCEPENIGMA BRCA1 specification v1.2 designates PS2 (de novo) as Not Applicable for BRCA1. Details ▾Hide ▴
PM1 VCEPENIGMA BRCA1 specification v1.2 designates PM1 as Not Applicable; domain-level considerations are captured through PP3/BP4/BP1 rules referencing clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857). Position 783 lies outside all three domains. Details ▾Hide ▴
Evidence considered
- PM1 not applicable per ENIGMA v1.2
- amino acid 783 is in the linker region outside RING
- coiled-coil
- and BRCT domains.
Sources
PM3 N/ASkipped — PM3 applies only to recessive disease (Fanconi Anemia phenotype with co-occurring BRCA1 variants); not applicable in the context of this heterozygous missense variant assessment without Fanconi Anemia phenotype data. Details ▾Hide ▴
No further detail was recorded.
PM4 VCEPSkipped — ENIGMA specification designates PM4 as Not Applicable; this is a missense substitution, not an in-frame deletion/insertion or stop-loss variant. Details ▾Hide ▴
No further detail was recorded.
PM5 N/AUnder ENIGMA BRCA1 specification, PM5 is repurposed for protein termination codon (PTC) variants in exons where a different proven pathogenic PTC variant has been observed, used to justify additional weight for PTC variants annotated as PVS1. This is a missense variant (p.Ile783Val); classic same-residue missense PM5 is not applied under ENIGMA rules. Details ▾Hide ▴
Evidence considered
- Missense variant
- ENIGMA PM5 applies only to PTC/truncating variants
- not missense comparators.
Sources
cspec ↗pm5_candidates
PM6 VCEPENIGMA BRCA1 specification v1.2 designates PM6 (de novo) as Not Applicable for BRCA1. Details ▾Hide ▴
PP2 VCEPENIGMA BRCA1 specification v1.2 designates PP2 as Not Applicable for BRCA1. Details ▾Hide ▴
PP5 VCEPENIGMA BRCA1 specification v1.2 designates PP5 as Not Applicable for BRCA1. ClinVar classification alone is not used as independent evidence under ENIGMA rules. Details ▾Hide ▴
BP2 VCEPENIGMA BRCA1 specification v1.2 designates BP2 as Not Applicable for BRCA1. Details ▾Hide ▴
BP3 VCEPSkipped — ENIGMA specification captures in-frame indel considerations through other criteria; not applicable to this missense substitution. Details ▾Hide ▴
No further detail was recorded.
BP6 VCEPENIGMA BRCA1 specification v1.2 designates BP6 as Not Applicable for BRCA1. Details ▾Hide ▴
PS5 N/APS5 is not defined in the ENIGMA BRCA1 specification v1.2. Details ▾Hide ▴
Identifiers
- Gene
- BRCA1
- Transcript
- NM_007294.4
- Coding (HGVS c.)
- NM_007294.4:c.2347A>G
- Protein (HGVS p.)
- NP_009225.1:p.(Ile783Val)
- GRCh38
- chr17:43093184 T>C
- GRCh37
- chr17:41245201 T>C
- ClinVar
- 4856577, 4529920, 2752887, 649341, 479222, 54541
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
18 / 1,613,836 alleles
AF 1.12e-05 · 0 homozygotes · FAF 0.000223
gnomAD v2.1
18 / 250,738 alleles
AF 7.18e-05 · 0 homozygotes · FAF 0.000632
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.1e-05 · 18 / 1,613,836 alleles · 0 hom · FAF 0.00022
| East Asian16 / 44,886 | 0.00036 |
| Remaining individuals2 / 62,478 | 3.2e-05 |
0 alternate alleles recorded in 8 other groups: Admixed American, European (Finnish), Amish, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American, European (non-Finnish).
gnomAD v2.1
AF 7.2e-05 · 18 / 250,738 alleles · 0 hom · FAF 0.00063
| East Asian18 / 18,394 | 0.00098 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.11535e-05; MAF= 0.00112%, 18/1613836 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000356459; MAF= 0.03565%, 16/44886 alleles, homozygotes = 0); grpmax FAF= 0.00022308.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.17881e-05; MAF= 0.00718%, 18/250738 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.00097858; MAF= 0.09786%, 18/18394 alleles, homozygotes = 0); grpmax FAF= 0.00063201.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.240
- BayesDel
- -0.316
How the predictions were used
PP3 ENIGMA PP3 applies to missense variants inside a clinically important functional domain with BayesDel ≥0.28, or when SpliceAI ≥0.2. Position 783 is outside all three ENIGMA domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857). BayesDel score is -0.316 (below 0.28 threshold). SpliceAI max delta is 0.0 (below 0.2 threshold). Neither criterion is satisfied. Details ▾Hide ▴
Evidence considered
- Position 783 outside functional domains
- BayesDel=-0.316 (<0.28)
- SpliceAI=0.0 (<0.2). No predicted pathogenic impact.
Sources
spliceai ↗bayesdel
BP4 ENIGMA BP4 applies to missense variants inside a clinically important functional domain with no predicted impact via protein change or splicing (BayesDel ≤0.15 AND SpliceAI ≤0.1). Position 783 is outside all three ENIGMA domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857). BP4 does not apply to variants outside these domains under ENIGMA rules; domain-external missense variants are captured by BP1 instead. Details ▾Hide ▴
Evidence considered
- Position 783 outside ENIGMA functional domains
- BP4 prerequisite (inside domain) not satisfied.
Sources
BP7 ENIGMA BP7_Strong (RNA) requires well-established functional studies showing no damaging effect on mRNA transcript profile (mRNA assay only). BS3_Strong is applied for protein-level functional neutrality; BP7 requires separate mRNA-level evidence. No mRNA-specific splicing or transcript assay data is available for this variant. SpliceAI predicts no splicing impact (max delta=0.0), but BP7 under ENIGMA requires experimental mRNA data, not predictions alone. BP7_Supporting applies only to silent or intronic variants, not missense substitutions. Details ▾Hide ▴
Evidence considered
- No mRNA-specific functional assay data available
- SpliceAI=0.0 is predictive but BP7 requires experimental mRNA evidence. BS3 already captures protein-level functional data.
Still missing
- mRNA transcript analysis could provide independent BP7 evidence if performed.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.24. BayesDel score = -0.316337.
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 15385441 ↗Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition.Pavlicek A et al. · 2004Pavlicek et al. 2004 analyzed BRCA1 locus evolution across primate species to identify regions under selective pressure relevant to cancer predisposition. NM_007294.4:c.2347A>G (p.Ile783Val) was not identified in this paper.Does not name this variant
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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. · 2005Judkins et al. 2005 described an approach using embryonic lethal phenotypes to characterize BRCA1 variants found in trans with known deleterious mutations. NM_007294.4:c.2347A>G (p.Ile783Val) was not identified in this paper.Does not name this variant
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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.Richards et al. 2015 (ACMG/AMP standards and guidelines) provides the generic framework for sequence variant interpretation. This is the foundational ACMG/AMP guideline document; NM_007294.4:c.2347A>G is not individually discussed.Does not name this variant
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PMID 30702160 ↗Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients.Bhaskaran SP et al. · 2019Bhaskaran et al. 2019 reported on ethnic-specific germline BRCA1/2 variation in over 30,000 Chinese hereditary breast and ovarian cancer patients. NM_007294.4:c.2347A>G (p.Ile783Val) was not individually reported in this study.Does not name this variant
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PMID 31911673 ↗Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots".Dines JN et al. · 2020Dines et al. 2020 analyzed BRCA1/2 missense variant coldspots using a Bayesian approach to identify regions tolerant to missense variation. NM_007294.4:c.2347A>G (p.Ile783Val) was not individually discussed.Does not name this variant
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PMID 34326862 ↗Analysis of Sequence and Copy Number Variants in Canadian Patient Cohort With Familial Cancer Syndromes Using a Unique Next Generation Sequencing Based Approach.Bhai P et al. · 2021Bhai et al. 2021 analyzed sequence and copy number variants in a Canadian familial cancer cohort using NGS-based approaches. NM_007294.4:c.2347A>G (p.Ile783Val) was not identified in this paper.Does not name this variant
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PMID 12692171 ↗American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility.ASCO 2003 policy statement update on genetic testing for cancer susceptibility. This is a clinical practice guideline document; NM_007294.4:c.2347A>G is not discussed.Does not name this variant
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PMID 17392385 ↗American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography.Saslow et al. 2007 (ACS guidelines for breast screening with MRI). This is a screening guideline document; NM_007294.4:c.2347A>G is not discussed.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Nykamp et al. 2017 (Sherloc refinement of ACMG-AMP criteria). This is a variant classification framework paper; NM_007294.4:c.2347A>G is not individually discussed.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
18 / 1,613,836 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
5 Benign · 3 Likely benign · 2 Uncertain significance · 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/54541/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-41245201-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-43093184-T-C?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/17-43093184-T-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_007294.4%3Ac.2347…
- OncoKB ↗www.oncokb.org/gene/BRCA1/I783V
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA1+c.2347A%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= 1.11535e-05; MAF= 0.00112%, 18/1613836 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000356459; MAF= 0.03565%, 16/44886 alleles, homozygotes = 0); grpmax FAF= 0.00022308.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.17881e-05; MAF= 0.00718%, 18/250738 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.00097858; MAF= 0.09786%, 18/18394 alleles, homozygotes = 0); grpmax FAF= 0.00063201.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Benign (5 clinical laboratories) and as Likely benign (3 clinical laboratories) and as Uncertain significance (2 clinical laboratories) and as benign (1 clinical laboratory). (ClinVarID = 54541)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.24. BayesDel score = -0.316337.
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.