The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!


Variant: NM_007294.4(BRCA1):c.81-11del

CA003895

37699 (ClinVar)

Gene: BRCA1
Condition: BRCA1-related cancer predisposition
Inheritance Mode: Autosomal dominant inheritance
UUID: 103a51b8-d098-4844-b998-328ce4a4acb7

HGVS expressions

NM_007294.4:c.81-11del
NM_007294.4(BRCA1):c.81-11del
NC_000017.11:g.43115790del
CM000679.2:g.43115790del
NC_000017.10:g.41267807del
CM000679.1:g.41267807del
NC_000017.9:g.38521333del
NG_005905.2:g.102194del
ENST00000354071.8:n.145-11del
ENST00000461574.2:c.81-11del
ENST00000470026.6:c.81-11del
ENST00000473961.6:c.81-11del
ENST00000476777.6:c.81-11del
ENST00000477152.6:c.81-11del
ENST00000478531.6:c.81-11del
ENST00000489037.2:c.81-11del
ENST00000493919.6:c.-8+8227del
ENST00000494123.6:c.81-11del
ENST00000497488.2:c.-219+9481del
ENST00000618469.2:c.81-11del
ENST00000634433.2:c.81-11del
ENST00000644379.2:c.81-11del
ENST00000644555.2:c.-61-11del
ENST00000652672.2:c.-61-11del
ENST00000484087.6:c.81-11del
ENST00000700182.1:c.81-11del
ENST00000700183.1:c.81-11del
ENST00000700184.1:n.324-11del
ENST00000700185.1:n.200-11del
ENST00000357654.9:c.81-11del
ENST00000471181.7:c.81-11del
ENST00000642945.1:c.81-11del
ENST00000644555.1:c.-61-11del
ENST00000652672.1:c.-61-11del
ENST00000352993.7:c.81-11del
ENST00000354071.7:c.81-11del
ENST00000357654.7:c.81-11del
ENST00000461221.5:c.81-11del
ENST00000461798.5:c.81-11del
ENST00000468300.5:c.81-11del
ENST00000470026.5:c.81-11del
ENST00000471181.6:c.81-11del
ENST00000476777.5:c.81-11del
ENST00000477152.5:c.81-11del
ENST00000478531.5:c.81-11del
ENST00000489037.1:c.81-11del
ENST00000491747.6:c.81-11del
ENST00000492859.5:c.81-11del
ENST00000493795.5:c.-8+8227del
ENST00000493919.5:c.-8+8227del
ENST00000494123.5:c.81-11del
ENST00000497488.1:c.-219+9481del
ENST00000586385.5:c.4+9392del
ENST00000591534.5:c.-44+9481del
ENST00000591849.5:c.-99+9481del
ENST00000634433.1:c.81-11del
NM_007294.3:c.81-11del
NM_007297.3:c.-8+8227del
NM_007298.3:c.81-11del
NM_007299.3:c.81-11del
NM_007300.3:c.81-11del
NR_027676.1:n.242-11del
NM_007297.4:c.-8+8227del
NM_007299.4:c.81-11del
NM_007300.4:c.81-11del
NR_027676.2:n.283-11del

Benign

Met criteria codes 3
BP4 BP7_Strong BP5_Strong
Not Met criteria codes 3
PM2 BA1 BS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen ENIGMA BRCA1 and BRCA2 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for BRCA1 Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
ENIGMA BRCA1 and BRCA2 VCEP
The c.81-11del variant is an intronic variant occurring in intron 2 of the BRCA1 gene. This variant is present in gnomAD v2.1 (exomes only, non-cancer subset) or gnomAD v3.1 (non-cancer subset) but is below the ENIGMA BRCA1/2 VCEP threshold >0.00002 for BS1_Supporting (PM2_Supporting, BS1, and BA1 are not met). This BRCA1 intronic variant is outside of the native donor and acceptor 1,2 splice sites, and SpliceAI predictor score of 0.00 suggests that the variant has no impact on splicing (score threshold <0.10) (BP4 met). This is an intronic variant, and mRNA experimental analysis indicates no impact on splicing (PMID: 21735045), considered strong evidence against pathogenicity (BP7_Strong (RNA)). Multifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 0.00131 (based on Co-occurrence LR=0.0406; Family History LR=0.0321), below the threshold for Very strong benign evidence (LR <0.00285) (BP5_Very strong met; (PMID: 17924331)). In summary, this variant meets the criteria to be classified as a Benign variant for BRCA1-related cancer predisposition based on the ACMG/AMP criteria applied as specified by the ENIGMA BRCA1/2 VCEP (BP4, BP7_Strong (RNA), BP5_Very strong).
Met criteria codes
BP4
This BRCA1 intronic variant is outside of the native donor and acceptor 1,2 splice sites, and SpliceAI predictor score of 0.00 suggests that the variant has no impact on splicing (score threshold <0.10) (BP4 met).
BP7_Strong
This is an intronic variant, and mRNA experimental analysis indicates no impact on splicing (PMID: 21735045), considered strong evidence against pathogenicity (BP7_Strong (RNA)).
BP5_Strong
Multifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 0.00131 (based on Co-occurrence LR=0.0406; Family History LR=0.0321), below the threshold for Very strong benign evidence (LR <0.00285) (BP5_Very strong met; (PMID: 17924331).
Not Met criteria codes
PM2
This variant is present in gnomAD v2.1 (exomes only, non-cancer subset) or gnomAD v3.1 (non-cancer subset) but is below the ENIGMA BRCA1/2 VCEP threshold >0.00002 for BS1_Supporting (PM2_Supporting, BS1, and BA1 are not met).
BA1
This variant is present in gnomAD v2.1 (exomes only, non-cancer subset) or gnomAD v3.1 (non-cancer subset) but is below the ENIGMA BRCA1/2 VCEP threshold >0.00002 for BS1_Supporting (PM2_Supporting, BS1, and BA1 are not met).
BS1
This variant is present in gnomAD v2.1 (exomes only, non-cancer subset) or gnomAD v3.1 (non-cancer subset) but is below the ENIGMA BRCA1/2 VCEP threshold >0.00002 for BS1_Supporting (PM2_Supporting, BS1, and BA1 are not met).
Approved on: 2024-06-12
Published on: 2024-06-12
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