About BRCA1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA1 c.4065_4068del, p.(Asn1355LysfsTer10)
Classification
Pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is pathogenic. Select a step to read what it means.
Pathogenic.A pathogenic 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: 4
Benign evidence criteria: 0
Pathogenic criteria applied · 4
PVS1Very strong
PVS1 · very strong
This variant is a frameshift deletion, NM_007294.4:c.4065_4068del, predicted to create p.(Asn1355LysfsTer10) / p.(N1355Kfs*10). It lies in BRCA1 exon 10(11), where the ENIGMA BRCA1 Table 4 assigns PVS1 for protein-truncating variants, and BRCA1 loss of function is an established disease mechanism in the official gene-specific framework.
PM5Strong
PM5 · strong
In the BRCA1 ENIGMA framework, PM5 is repurposed for protein-truncating variants rather than classic same-residue missense logic. This frameshift lies in BRCA1 exon 10(11), and ENIGMA Table 4 assigns PM5_Strong (PTC) for truncating variants in this exon.
PP4Strong
PP4 · strong
The BRCA1 clinical-history likelihood-ratio workbook contains this deletion as c.4065_4068delTCAA with 37 probands and LR 6590.9969. This exceeds the ENIGMA PP4 threshold for pathogenic clinical-history evidence and supports PP4.
PP5Supporting
PP5 · supporting
Expert panel Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) classified as Pathogenic.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Pathogenic
ENIGMA BRCA1/BRCA2 Specification v1.2 final-classification framework (Table 3 override captured in final_classification_framework; ACMG/AMP 2015 with ENIGMA adaptations).
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
53 / 1,613,548 alleles
gnomAD v4.1: 53 / 1,613,548 alleles. Recorded AF 3.28469e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.19596e-05; MAF= 0.00120%, 3/250844 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.28106e-05; MAF= 0.00328%, 1/30478 alleles, homozygotes = 0); grpmax FAF= 2.93e-06.
No listed criterion applied
SpliceAI score
0.140 maximum delta
Recorded SpliceAI maximum delta score: 0.140. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
52 reported laboratory submissions
51 Pathogenic · 1 Likely pathogenic.
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.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
2 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV99066383, n = 2 times).
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.
28 criteria with recorded statuses: 4 met · 4 not met · 5 not assessed · 15 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The BRCA1 NM_007294.4:c.4065_4068del (NP_009225.1:p.(Asn1355LysfsTer10), p.(N1355Kfs*10)) variant has been reported in ClinVar as Pathogenic by the ENIGMA expert panel and by multiple clinical laboratories.
This variant is present at very low frequency in gnomAD v2.1 (3/250844 alleles; AF 1.19596e-05, 0.00120%; grpmax FAF 2.93e-06), which is below the BRCA1 BA1 and BS1 thresholds but means the variant is not absent from controls, so PM2 is not met.
The BRCA1 clinical-history likelihood-ratio dataset lists this deletion as c.4065_4068delTCAA in 37 probands with LR 6590.9969, supporting pathogenic clinical-history evidence under the ENIGMA BRCA1 framework.
This frameshift lies in BRCA1 exon 10(11) and predicts a premature stop codon at residue 1364; the ENIGMA BRCA1 exon-specific Table 4 supports PVS1 and PM5_Strong (PTC) for truncating variants in this exon.
No criteria match.
Met · 4
PVS1 Very strongThis variant is a frameshift deletion, NM_007294.4:c.4065_4068del, predicted to create p.(Asn1355LysfsTer10) / p.(N1355Kfs*10). It lies in BRCA1 exon 10(11), where the ENIGMA BRCA1 Table 4 assigns PVS1 for protein-truncating variants, and BRCA1 loss of function is an established disease mechanism in the official gene-specific framework. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification PVS1 for null variants, with exon-specific weighting from Table 4.
Evidence considered
- Frameshift consequence p.(Asn1355LysfsTer10) / p.(N1355Kfs*10)
- Variant maps to BRCA1 exon 10(11)
- BRCA1 loss of function supported as disease mechanism
- ENIGMA Table 4 PTC row for exon 10(11) = PVS1
Sources
PM5 StrongIn the BRCA1 ENIGMA framework, PM5 is repurposed for protein-truncating variants rather than classic same-residue missense logic. This frameshift lies in BRCA1 exon 10(11), and ENIGMA Table 4 assigns PM5_Strong (PTC) for truncating variants in this exon. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification PM5_PTC for truncating variants in eligible exons per Table 4.
Evidence considered
- PM5 mode is PTC gene-specific
- not classic same-residue missense
- Variant maps to BRCA1 exon 10(11)
- ENIGMA Table 4 exon 10(11) PTC row = PM5_Strong (PTC)
Sources
PP4 StrongThe BRCA1 clinical-history likelihood-ratio workbook contains this deletion as c.4065_4068delTCAA with 37 probands and LR 6590.9969. This exceeds the ENIGMA PP4 threshold for pathogenic clinical-history evidence and supports PP4. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification PP4 uses calibrated clinical-history likelihood ratios; LR >= 18.7 supports at least Strong pathogenic clinical-history evidence.
Evidence considered
- Variant matched as c.4065_4068delTCAA in BRCA1 LR workbook
- N_Probands = 37
- LR = 6590.996910273256
Sources
vcep_pmid_31853058_brca1_clinical_history_lrvcep_pmid_31853058_li_2020_geneticsinmedicinePMID:31853058 ↗vcep_specifications_v1_2_2024_11_18
PP5 SupportingExpert panel Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) classified as Pathogenic. Details ▾Hide ▴
Not met · 4 · evaluated, threshold not reached
PM2 This variant is not absent from controls, so PM2 is not met. In gnomAD v2.1 it is present at 3/250844 alleles (AF 1.19596e-05; 0.00120%), with grpmax FAF 2.93e-06 and no homozygotes. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification PM2_Supporting requires absence from controls in gnomAD with adequate coverage.
Evidence considered
- gnomAD v2.1 AC 3/AN 250844
- AF 1.19596e-05
- grpmax FAF 2.93e-06
- 0 homozygotes
Sources
BA1 BA1 is not met because the highest observed grpmax FAF is 2.93e-06 in gnomAD v2.1, which is well below the BRCA1 BA1 threshold of 0.001. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification BA1 requires FAF > 0.001 in a non-founder population.
Evidence considered
- gnomAD v2.1 grpmax FAF 2.93e-06
- BA1 threshold 0.001
Sources
BS1 BS1 is not met because the highest observed grpmax FAF is 2.93e-06 in gnomAD v2.1, below both the BRCA1 BS1 supporting threshold of 0.00002 and strong threshold of 0.0001. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification BS1 uses FAF thresholds > 0.00002 and > 0.0001.
Evidence considered
- gnomAD v2.1 grpmax FAF 2.93e-06
- BS1 supporting threshold 0.00002
- BS1 strong threshold 0.0001
Sources
BP5 BP5 is not met because the available BRCA1 clinical-history likelihood ratio is strongly in the pathogenic direction rather than the benign direction. The matched workbook entry for c.4065_4068delTCAA shows LR 6590.9969 in 37 probands, which is far above the benign BP5 thresholds. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification BP5 uses benign-direction clinical-history likelihood ratios.
Evidence considered
- N_Probands = 37
- LR = 6590.996910273256
- BP5 requires low LR against pathogenicity
Sources
Not assessed · 5 · no assessment recorded
PS4 The variant has been reported in ClinVar and older literature sources, but no validated BRCA1 case-control analysis with odds ratio and confidence interval meeting the ENIGMA PS4 threshold was identified. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification PS4 requires significant enrichment in affected individuals versus controls.
Evidence considered
- ClinVar expert-panel pathogenic classification
- Older case-report/case-series PMIDs present in source registry
- No qualifying case-control statistic found
Still missing
- No eligible case-control dataset with OR >= 4 and lower confidence interval excluding 2.0 was identified.
- Published affected-case counts were not assembled into a PS4-eligible analysis.
Sources
clinvar ↗vcep_specifications_v1_2_2024_11_18PMID:10699917 ↗PMID:11802209 ↗PMID:14757871 ↗PMID:17018160 ↗PMID:21559243 ↗
PM3 No evidence was identified that this variant was observed with another BRCA1 pathogenic variant in a patient with a phenotype consistent with BRCA1-related Fanconi anemia, so PM3 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification PM3 is reserved for BRCA1/2-related Fanconi anemia evidence.
Evidence considered
- No Fanconi anemia-specific case evidence located
Still missing
- No biallelic BRCA1 Fanconi-anemia case data identified.
- No phase-confirmed co-occurrence data identified.
Sources
cspec ↗vcep_specifications_v1_2_2024_11_18
PP1 No quantitative co-segregation data were identified for this variant, so PP1 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification PP1 requires quantitative co-segregation evidence.
Evidence considered
- No variant-specific segregation LR located
Still missing
- No pedigree-based likelihood ratio was identified.
- No informative family segregation dataset was identified.
Sources
BS2 No evidence was identified showing this variant in individuals without features of BRCA1-related Fanconi anemia under the BRCA1 BS2 point-based framework, so BS2 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification BS2 uses a point-based framework tied to absence of recessive disease features.
Evidence considered
- No BS2-specific proband data located
Still missing
- No BS2 point-based proband evidence identified.
- No phenotype-documented unaffected or non-Fanconi cases identified for BS2 scoring.
Sources
cspec ↗vcep_specifications_v1_2_2024_11_18
BS4 No quantitative lack-of-segregation evidence was identified for this variant, so BS4 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification BS4 requires quantitative lack-of-segregation evidence.
Evidence considered
- No variant-specific non-segregation LR located
Still missing
- No pedigree-based LR against pathogenicity was identified.
- No affected non-carrier or comparable discordant segregation dataset was identified.
Sources
Not applicable · 15· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 is not applicable because this variant is a frameshift protein-truncating deletion rather than a missense change or a same-splice-effect comparison variant. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification PS1 applies to missense or matched splicing-impact comparators.
Evidence considered
- Frameshift deletion
- not missense
- No same-splice comparator evidence identified
Sources
cspec ↗vcep_specifications_v1_2_2024_11_18
PS2 VCEPPS2 is not applicable in this BRCA1 VCEP framework. Details ▾Hide ▴
VCEP rule
BRCA1 ENIGMA CSPEC applicability setting.
Evidence considered
- CSPEC marks PS2 not applicable
Sources
PS3 N/APS3 was not applied because the BRCA1 curated functional assay resources are intended for specific missense, synonymous, or splice-impact variants, and no calibrated protein functional assay result for this frameshift deletion was identified. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification PS3 uses calibrated functional assay evidence.
Evidence considered
- Variant is frameshift
- not a Table 9 missense/synonymous entry
- No calibrated variant-specific functional assay located
Sources
PM1 VCEPPM1 is not applicable in this BRCA1 VCEP framework. Details ▾Hide ▴
VCEP rule
BRCA1 ENIGMA CSPEC applicability setting.
Evidence considered
- CSPEC marks PM1 not applicable
Sources
PM4 VCEPPM4 is not applicable in this BRCA1 VCEP framework. Details ▾Hide ▴
VCEP rule
BRCA1 ENIGMA CSPEC applicability setting.
Evidence considered
- CSPEC marks PM4 not applicable
Sources
PM6 VCEPPM6 is not applicable in this BRCA1 VCEP framework. Details ▾Hide ▴
VCEP rule
BRCA1 ENIGMA CSPEC applicability setting.
Evidence considered
- CSPEC marks PM6 not applicable
Sources
PP2 VCEPPP2 is not applicable in this BRCA1 VCEP framework. Details ▾Hide ▴
VCEP rule
BRCA1 ENIGMA CSPEC applicability setting.
Evidence considered
- CSPEC marks PP2 not applicable
Sources
PP3 N/APP3 was not applied because this is a frameshift deletion. The BRCA1 computational PP3 rule is designed for missense, in-frame, silent, or non-canonical intronic variants; REVEL and BayesDel were not available for this deletion, and SpliceAI showed only a max delta score of 0.14, below the BRCA1 PP3 splice threshold of 0.2. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification PP3 applies to specified missense/in-frame/splicing scenarios, with SpliceAI >= 0.2 for splice prediction.
Evidence considered
- Variant type = frameshift deletion
- REVEL skipped for non-SNV
- BayesDel skipped for non-SNV
- SpliceAI max delta score 0.14
Sources
BS3 N/ABS3 was not applied because no calibrated benign functional assay result was identified for this frameshift deletion, and the BRCA1 curated BS3 resources are directed mainly to specific missense, synonymous, or splice-impact variants. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification BS3 uses calibrated functional assay evidence.
Evidence considered
- Variant is frameshift
- not a listed curated BS3 assay target
- No variant-specific benign functional assay result identified
Sources
BP1 N/ABP1 is not applicable because this variant is a frameshift deletion, whereas the BRCA1 BP1 rule applies to silent, missense, or in-frame variants outside key functional domains with no splice effect predicted. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification BP1 is restricted to silent, missense, and in-frame variants.
Evidence considered
- Frameshift deletion
Sources
BP2 VCEPBP2 is not applicable in this BRCA1 VCEP framework. Details ▾Hide ▴
VCEP rule
BRCA1 ENIGMA CSPEC applicability setting.
Evidence considered
- CSPEC marks BP2 not applicable
Sources
BP3 VCEPBP3 is not applicable in this BRCA1 VCEP framework. Details ▾Hide ▴
VCEP rule
BRCA1 ENIGMA CSPEC applicability setting.
Evidence considered
- CSPEC marks BP3 not applicable
Sources
BP4 N/ABP4 was not applied because this is a frameshift deletion. The BRCA1 BP4 rule is intended for missense, in-frame, silent, or non-canonical intronic variants with benign computational evidence; REVEL and BayesDel were not available for this deletion, and SpliceAI max delta score was 0.14. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification BP4 applies to specified missense/in-frame/silent/intronic scenarios.
Evidence considered
- Variant type = frameshift deletion
- REVEL skipped for non-SNV
- BayesDel skipped for non-SNV
- SpliceAI max delta score 0.14
Sources
BP6 VCEPBP6 is not applicable in this BRCA1 VCEP framework. Details ▾Hide ▴
VCEP rule
BRCA1 ENIGMA CSPEC applicability setting.
Evidence considered
- CSPEC marks BP6 not applicable
Sources
BP7 N/ABP7 is not applicable because this variant is a frameshift coding deletion rather than a silent or eligible intronic variant. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification BP7 applies to silent or eligible intronic variants, with or without RNA evidence depending on context.
Evidence considered
- Frameshift coding deletion
- SpliceAI max delta score 0.14
Sources
Identifiers
- Gene
- BRCA1
- Transcript
- NM_007294.4
- Coding (HGVS c.)
- NM_007294.4:c.4065_4068del
- Protein (HGVS p.)
- NP_009225.1:p.(Asn1355LysfsTer10)
- GRCh38
- chr17:43091462 CTTGA>C
- GRCh37
- chr17:41243479 CTTGA>C
- ClinVar
- 17674, 409338
- COSMIC
- COSV99066383
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
53 / 1,613,548 alleles
AF 3.28e-05 · 0 homozygotes · FAF 3.18e-05
gnomAD v2.1
3 / 250,844 alleles
AF 1.2e-05 · 0 homozygotes · FAF 2.93e-06
By genetic ancestry
gnomAD v4.1
AF 3.3e-05 · 53 / 1,613,548 alleles · 0 hom · FAF 3.2e-05
| European (non-Finnish)49 / 1,179,898 | 4.2e-05 |
| South Asian3 / 90,982 | 3.3e-05 |
| East Asian1 / 44,886 | 2.2e-05 |
0 alternate alleles recorded in 7 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, Middle Eastern, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 1.2e-05 · 3 / 250,844 alleles · 0 hom · FAF 2.9e-06
| South Asian1 / 30,478 | 3.3e-05 |
| European (non-Finnish)2 / 113,544 | 1.8e-05 |
0 alternate alleles recorded in 6 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 3.28469e-05; MAF= 0.00328%, 53/1613548 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.1529e-05; MAF= 0.00415%, 49/1179898 alleles, homozygotes = 0); grpmax FAF= 3.179e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.19596e-05; MAF= 0.00120%, 3/250844 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.28106e-05; MAF= 0.00328%, 1/30478 alleles, homozygotes = 0); grpmax FAF= 2.93e-06.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 N/APP3 was not applied because this is a frameshift deletion. The BRCA1 computational PP3 rule is designed for missense, in-frame, silent, or non-canonical intronic variants; REVEL and BayesDel were not available for this deletion, and SpliceAI showed only a max delta score of 0.14, below the BRCA1 PP3 splice threshold of 0.2. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification PP3 applies to specified missense/in-frame/splicing scenarios, with SpliceAI >= 0.2 for splice prediction.
Evidence considered
- Variant type = frameshift deletion
- REVEL skipped for non-SNV
- BayesDel skipped for non-SNV
- SpliceAI max delta score 0.14
Sources
BP4 N/ABP4 was not applied because this is a frameshift deletion. The BRCA1 BP4 rule is intended for missense, in-frame, silent, or non-canonical intronic variants with benign computational evidence; REVEL and BayesDel were not available for this deletion, and SpliceAI max delta score was 0.14. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification BP4 applies to specified missense/in-frame/silent/intronic scenarios.
Evidence considered
- Variant type = frameshift deletion
- REVEL skipped for non-SNV
- BayesDel skipped for non-SNV
- SpliceAI max delta score 0.14
Sources
BP7 N/ABP7 is not applicable because this variant is a frameshift coding deletion rather than a silent or eligible intronic variant. Details ▾Hide ▴
Rule
ENIGMA BRCA1/BRCA2 specification BP7 applies to silent or eligible intronic variants, with or without RNA evidence depending on context.
Evidence considered
- Frameshift coding deletion
- SpliceAI max delta score 0.14
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.14).
10 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
-
PMID 11358863 ↗Tumorigenesis in mice carrying a truncating Brca1 mutation.No paper-specific finding is recorded.
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PMID 12483515 ↗The cancer connection: BRCA1 and BRCA2 tumor suppression in mice and humans.No paper-specific finding is recorded.
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PMID 12947386 ↗Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation.No paper-specific finding is recorded.
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PMID 20608970 ↗BRCA1 16 years later: risk-associated BRCA1 mutations and their functional implications.No paper-specific finding is recorded.
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PMID 10699917 ↗Detection of BRCA1 and BRCA2 mutations in breast cancer families by a comprehensive two-stage screening procedure.No paper-specific finding is recorded.
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PMID 11802209 ↗Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population.No paper-specific finding is recorded.
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PMID 14757871 ↗Haplotype and cancer risk analysis of two common mutations, BRCA1 4184del4 and BRCA2 2157delG, in high risk northwest England breast/ovarian families.No paper-specific finding is recorded.
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PMID 17018160 ↗Contribution of germline BRCA1 and BRCA2 sequence alterations to breast cancer in Northern India.No paper-specific finding is recorded.
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PMID 21559243 ↗Breast and Ovarian Cancer Risk due to Prevalence of BRCA1 and BRCA2 Variants in Pakistani Population: A Pakistani Database Report.No 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
53 / 1,613,548 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.140
Open source ↗
ClinVar
51 Pathogenic · 1 Likely 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/17674/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-41243479-CTTGA-C?dataset=g…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-43091462-CTTGA-C?datase…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_007294.4%3Ac.4065…
- OncoKB ↗www.oncokb.org/gene/BRCA1/N1355Kfs*10
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=144951769
- 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= 3.28469e-05; MAF= 0.00328%, 53/1613548 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.1529e-05; MAF= 0.00415%, 49/1179898 alleles, homozygotes = 0); grpmax FAF= 3.179e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.19596e-05; MAF= 0.00120%, 3/250844 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.28106e-05; MAF= 0.00328%, 1/30478 alleles, homozygotes = 0); grpmax FAF= 2.93e-06.
ClinVar
This variant has been reported in ClinVar as Pathogenic (51 clinical laboratories) and as Likely pathogenic (1 clinical laboratory) and as Pathogenic by Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) (expert panel). (ClinVarID = 17674)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.14).
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 previously been reported in somatic cancers (COSMIC; COSV99066383, n = 2 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.