ClinVar

NM_007294.4(BRCA1):c.212+1G>A

Gene:

BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

• Chr17: 43106455 (on Assembly GRCh38)
• Chr17: 41258472 (on Assembly GRCh37)

Preferred name:

NM_007294.4(BRCA1):c.212+1G>A

Other names:

IVS5+1G>Adel22; U14680.1:n.331+1G>A,del22

HGVS:

• NC_000017.11:g.43106455C>T
• NG_005905.2:g.111529G>A
• NM_007294.3:c.212+1G>A
• NM_007294.4:c.212+1G>A
• NM_007297.4:c.71+1G>A
• NM_007298.3:c.212+1G>A
• NM_007299.4:c.212+1G>A
• NM_007300.4:c.212+1G>A
• LRG_292t1:c.212+1G>A
• LRG_292:g.111529G>A
• NC_000017.10:g.41258472C>T
• U14680.1:n.331+1G>A

This HGVS expression did not pass validation

Nucleotide change:

IVS5+1G>A

Links:

Breast Cancer Information Core (BIC) (BRCA1): 331+1&base_change=G to A; dbSNP: rs80358042

NCBI 1000 Genomes Browser:

rs80358042

Molecular consequence:

• NM_007294.3:c.212+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
• NM_007294.4:c.212+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
• NM_007297.4:c.71+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
• NM_007298.3:c.212+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
• NM_007299.4:c.212+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
• NM_007300.4:c.212+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Functional consequence:

• cryptic splice donor activation [PubMedVariation Ontology: 0374] - Comment(s)
  • This substitution activates a cryptic donor splice site at the closest GT dinucleotide downstream. The junction of the truncated exon 5 with exon 6 results in a stop codon at amino acid 64.
• functionally_abnormal [Sequence Ontology: SO:0002218] - Comment(s)
  • The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.212+1G>A, a CANONICAL SPLICE variant, produced a function score of -1.42, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12.

Observations:

1