Evidence Repository
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 label mismatch: BRCA1 vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • cspecId property did not resolve into a valid CSPEC request: https://cspec.genome.network/cspec-priv/SequenceVariantInterpretation/id/1530970171!
  • cspec.ruleSetIri property did not resolve into a valid CSPEC request: https://cspec.genome.network/cspec-priv/RuleSet/id/1530970184!
  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_007294.4(BRCA1):c.5407-10G>A

CA003567

96950 (ClinVar)

Gene: BRCA1
Condition: BRCA1-related cancer predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 4d9ec722-990e-4186-984d-7c97c7e83195
Approved on: 2025-05-23
Published on: 2025-05-23

HGVS expressions

NM_007294.4:c.5407-10G>A
NM_007294.4(BRCA1):c.5407-10G>A
NC_000017.11:g.43047713C>T
CM000679.2:g.43047713C>T
NC_000017.10:g.41199730C>T
CM000679.1:g.41199730C>T
NC_000017.9:g.38453256C>T
NG_005905.2:g.170271G>A
ENST00000461574.2:c.5404-10G>A
ENST00000470026.6:c.5407-10G>A
ENST00000473961.6:c.5281-10G>A
ENST00000476777.6:c.5401-10G>A
ENST00000477152.6:c.5329-10G>A
ENST00000478531.6:c.2095-10G>A
ENST00000489037.2:c.5329-10G>A
ENST00000493919.6:c.1957-10G>A
ENST00000494123.6:c.5407-10G>A
ENST00000497488.2:c.4519-10G>A
ENST00000618469.2:c.5407-10G>A
ENST00000634433.2:c.5284-10G>A
ENST00000644379.2:c.5473-10G>A
ENST00000644555.2:c.1957-10G>A
ENST00000652672.2:c.5266-10G>A
ENST00000484087.6:c.1969-10G>A
ENST00000700081.1:n.1290-10G>A
ENST00000700082.1:n.761G>A
ENST00000357654.9:c.5407-10G>A
ENST00000471181.7:c.5470-10G>A
ENST00000644379.1:c.1794-10G>A
ENST00000352993.7:c.1981-10G>A
ENST00000357654.7:c.5407-10G>A
ENST00000461221.5:c.*5190-10G>A
ENST00000468300.5:c.2021-10G>A
ENST00000471181.6:c.5470-10G>A
ENST00000491747.6:c.2095-10G>A
ENST00000493795.5:c.5266-10G>A
ENST00000586385.5:c.337-10G>A
ENST00000591534.5:c.880-10G>A
ENST00000591849.5:c.106-10G>A
NM_007294.3:c.5407-10G>A
NM_007297.3:c.5266-10G>A
NM_007298.3:c.2095-10G>A
NM_007299.3:c.2021-10G>A
NM_007300.3:c.5470-10G>A
NR_027676.1:n.5543-10G>A
NM_007297.4:c.5266-10G>A
NM_007299.4:c.2021-10G>A
NM_007300.4:c.5470-10G>A
NR_027676.2:n.5584-10G>A
More

Likely Pathogenic

Met criteria codes 2
PVS1 PM2_Supporting
Not Met criteria codes 1
PS3

Evidence Links 3

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
ENIGMA BRCA1 and BRCA2 VCEP
The c.5407-10G>A variant is an intronic variant occurring in intron 21 of the BRCA1 gene. This variant is absent from gnomAD v2.1 (exomes only, non-cancer subset, read depth ≥25) and gnomAD v3.1 (non-cancer subset, read depth ≥25) (PM2_Supporting met). This variant is reported to result in aberrant mRNA splicing. RTPCR data demonstrated that the variant impacts splicing by retaining 8 basepairs of the adjacent intron resulting in a frameshift. (PMIDs 31143303, 35167739). Appropriate code strength determined by comparison of results to PVS1 decision tree and assessment of mRNA splicing data (PVS1 (RNA) met). This variant is reported by one calibrated study to exhibit intermediate protein function between benign and pathogenic control variants (PMIDs 30209399) (PS3 and BS3 not met). In summary, this variant meets the criteria to be classified as a Likely pathogenic variant for BRCA1-related cancer predisposition based on the ACMG/AMP criteria applied as specified by the ENIGMA BRCA1/2 VCEP (PVS1 (RNA), PM2_Supporting).
Met criteria codes
PVS1
This variant is reported to result in aberrant mRNA splicing. RTPCR data demonstrated that the variant impacts splicing by retaining 8 basepairs of the adjacent intron resulting in a frameshift. (PMIDs 31143303, 35167739). Appropriate code strength determined by comparison of results to PVS1 decision tree and assessment of mRNA splicing data (PVS1(RNA) met).
PM2_Supporting
This variant is absent from gnomAD v2.1 (exomes only, non-cancer subset, read depth ≥25) and gnomAD v3.1 (non-cancer subset, read depth ≥25) (PM2_Supporting met).
Not Met criteria codes
PS3
Reported by one calibrated study to exhibit intermediate protein function between benign and pathogenic control variants (PMIDs 30209399) (PS3|BS3 not met).
Intermediate function PubMed:30209399
RNA analyses have demonstrated this variant to result in an 8 nucleotide insertion resulting in frameshift and premature truncation of the final 27 amino acids in a region that is critical for protein function. Allele specific expression suggests a complete effect. PubMed:35167739
RNA analyses have demonstrated this variant to result in an 8 nucleotide insertion resulting in frameshift and premature truncation of the final 27 amino acids in a region that is critical for protein function. Allele specific expression suggests a complete effect. PubMed:31143303
Curation History
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