Submissions for variant NM_032043.3(BRIP1):c.1141-7_1141-3del

dbSNP: rs1060501744

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000477390	SCV000547274	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2023-10-09	criteria provided, single submitter	clinical testing	This sequence change falls in intron 8 of the BRIP1 gene. It does not directly change the encoded amino acid sequence of the BRIP1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 407815). Studies have shown that this variant is associated with altered splicing resulting in unknown protein product impact (Invitae). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV002451103	SCV002614761	uncertain significance	Hereditary cancer-predisposing syndrome	2022-03-28	criteria provided, single submitter	clinical testing	The c.1141-7_1141-3delCTTAT intronic variant, located in intron 7 of the BRIP1 gene, results from a deletion of 5 nucleotides within intron 7 of the BRIP1 gene. This nucleotide region is generally well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne	RCV003483619	SCV004231864	uncertain significance	Hereditary breast ovarian cancer syndrome	2024-01-09	criteria provided, single submitter	curation	. According to the ACMG standard criteria we chose these criteria: PP3 (supporting pathogenic): SpliceAI: Acceptor Loss 0.20 canonical splice site; Acceptor Gain 0.57 intronic -39 bp , BP7 (supporting benign): Splicing assay data demonstrating a variant is not associated with aberrantly spliced transcript(s) relative to transcript profiles in controls (s. Köln)
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492055	SCV004240383	uncertain significance	Breast and/or ovarian cancer	2023-02-17	criteria provided, single submitter	clinical testing