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
  • cspec.ruleSetIri property did not resolve into a valid CSPEC request: https://cspec.genome.network/cspec-priv/RuleSet/id/1530970184!
  • cspecId property did not resolve into a valid CSPEC request: https://cspec.genome.network/cspec-priv/SequenceVariantInterpretation/id/1530970171!
  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_007294.4(BRCA1):c.134+3A>T

CA658798847

531302 (ClinVar)

Gene: BRCA1
Condition: BRCA1-related cancer predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: a138bc91-7ca5-431f-beb4-82d9da393b45
Approved on: 2025-05-23
Published on: 2025-05-23

HGVS expressions

NM_007294.4:c.134+3A>T
NM_007294.4(BRCA1):c.134+3A>T
NC_000017.11:g.43115723T>A
CM000679.2:g.43115723T>A
NC_000017.10:g.41267740T>A
CM000679.1:g.41267740T>A
NC_000017.9:g.38521266T>A
NG_005905.2:g.102261A>T
ENST00000354071.8:n.198+3A>T
ENST00000461574.2:c.134+3A>T
ENST00000470026.6:c.134+3A>T
ENST00000473961.6:c.134+3A>T
ENST00000476777.6:c.134+3A>T
ENST00000477152.6:c.134+3A>T
ENST00000478531.6:c.134+3A>T
ENST00000489037.2:c.134+3A>T
ENST00000493919.6:c.-8+8294A>T
ENST00000494123.6:c.134+3A>T
ENST00000497488.2:c.-219+9548A>T
ENST00000618469.2:c.134+3A>T
ENST00000634433.2:c.134+3A>T
ENST00000644379.2:c.134+3A>T
ENST00000644555.2:c.-8+3A>T
ENST00000652672.2:c.-8+3A>T
ENST00000484087.6:c.134+3A>T
ENST00000700182.1:c.134+3A>T
ENST00000700183.1:c.134+3A>T
ENST00000700184.1:n.377+3A>T
ENST00000700185.1:n.253+3A>T
ENST00000357654.9:c.134+3A>T
ENST00000471181.7:c.134+3A>T
ENST00000642945.1:c.134+3A>T
ENST00000644555.1:c.-8+3A>T
ENST00000652672.1:c.-8+3A>T
ENST00000352993.7:c.134+3A>T
ENST00000354071.7:c.134+3A>T
ENST00000357654.7:c.134+3A>T
ENST00000461221.5:c.134+3A>T
ENST00000461798.5:c.134+3A>T
ENST00000468300.5:c.134+3A>T
ENST00000470026.5:c.134+3A>T
ENST00000471181.6:c.134+3A>T
ENST00000476777.5:c.134+3A>T
ENST00000477152.5:c.134+3A>T
ENST00000478531.5:c.134+3A>T
ENST00000489037.1:c.134+3A>T
ENST00000491747.6:c.134+3A>T
ENST00000492859.5:c.134+3A>T
ENST00000493795.5:c.-8+8294A>T
ENST00000493919.5:c.-8+8294A>T
ENST00000494123.5:c.134+3A>T
ENST00000497488.1:c.-219+9548A>T
ENST00000586385.5:c.4+9459A>T
ENST00000591534.5:c.-44+9548A>T
ENST00000591849.5:c.-99+9548A>T
ENST00000634433.1:c.134+3A>T
NM_007294.3:c.134+3A>T
NM_007297.3:c.-8+8294A>T
NM_007298.3:c.134+3A>T
NM_007299.3:c.134+3A>T
NM_007300.3:c.134+3A>T
NR_027676.1:n.295+3A>T
NM_007297.4:c.-8+8294A>T
NM_007299.4:c.134+3A>T
NM_007300.4:c.134+3A>T
NR_027676.2:n.336+3A>T
More

Likely Pathogenic

Met criteria codes 3
PM2_Supporting PS3 PP3
Not Met criteria codes 2
PVS1 BP7

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
ENIGMA BRCA1 and BRCA2 VCEP
The c.134+3A>T variant is an intronic variant occurring in intron 3 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 BRCA1 intronic variant is located outside of the native donor and acceptor 1,2 splice sites, and has a SpliceAI score of 0.83, predicting an impact on splicing (score threshold >0.20) (PP3 met). Intronic variant, functional data considered only from assays that measure effect via mRNA and protein. Reported by one calibrated study incorporating mRNA splicing effects to exhibit protein function similar to pathogenic control variants (PMID:30209399) (PS3 met). This variant is reported to result in aberrant mRNA splicing. RT-PCR and agarose gel electrophoresis demonstrated that the variant impacts splicing by exon 3 skipping (PMID: 32123317). The percent full-length and aberrant transcripts produced from the variant allele was not stated (PVS1 (RNA) and BP7_Strong (RNA) 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 (PM2_Supporting, PP3, PS3).
Met criteria codes
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).
PS3
Intronic variant, functional data considered only from assays that measure effect via mRNA and protein. Reported by one calibrated study incorporating mRNA splicing effects to exhibit protein function similar to pathogenic control variants (PMID:30209399) (PS3 met).
PP3
This BRCA1 intronic variant is located outside of the native donor and acceptor 1,2 splice sites, and has a SpliceAI score of 0.83, predicting an impact on splicing (score threshold >0.20) (PP3 met).
Not Met criteria codes
PVS1
This variant is reported to result in aberrant mRNA splicing. RT-PCR and agarose gel electrophoresis demonstrated that the variant impacts splicing by exon 3 skipping (PMID: 32123317). The percent full-length and aberrant transcripts produced from the variant allele was not stated (PVS1 (RNA) and BP7_Strong (RNA) not met).
BP7
This variant is reported to result in aberrant mRNA splicing. RT-PCR and agarose gel electrophoresis demonstrated that the variant impacts splicing by exon 3 skipping (PMID: 32123317). The percent full-length and aberrant transcripts produced from the variant allele was not stated (PVS1 (RNA) and BP7_Strong (RNA) not met).
Curation History
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