Submissions for variant NM_032043.3(BRIP1):c.627+3A>G

dbSNP: rs777434654

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000572650	SCV000668935	uncertain significance	Hereditary cancer-predisposing syndrome	2024-04-30	criteria provided, single submitter	clinical testing	The c.627+3A>G intronic variant results from an A to G substitution 3 nucleotides after coding exon 5 in the BRIP1 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. RNA studies have demonstrated that this alteration results in an incomplete splice defect; the clinical impact of this abnormal splicing is unknown at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV000572650	SCV000684293	uncertain significance	Hereditary cancer-predisposing syndrome	2020-01-21	criteria provided, single submitter	clinical testing	This variant causes an A>G nucleotide substitution at the +3 position of intron 6 of the BRIP1 gene. Splice site prediction tools suggest that this variant may impact RNA splicing. However, this prediction has not been confirmed in published RNA studies. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000802653	SCV000942494	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2023-07-10	criteria provided, single submitter	clinical testing	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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 483180). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 6 of the BRIP1 gene. It does not directly change the encoded amino acid sequence of the BRIP1 protein. It affects a nucleotide within the consensus splice site.