ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.379+4_379+5del (rs773332695)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165685 SCV000216423 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000462582 SCV000547275 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-08-06 criteria provided, single submitter clinical testing This sequence change falls in intron 4 of the BRIP1 gene. It does not directly change the encoded amino acid sequence of the BRIP1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs773332695, ExAC 0.01%). This variant has not been reported in the literature in individuals with BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 186147). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
GeneDx RCV000480389 SCV000569684 uncertain significance not provided 2017-11-28 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.379+4_379+5delAT or IVS4+4_IVS4+5delAT, and consists of a deletion of two nucleotides at the +4 and +5 positions of intron 4 of the BRIP1 gene. The normal sequence with the bases that are deleted in brackets is Ggta[delat]ttat, where the capital letters are exonic and lowercase are intronic. In silico splicing models are inconsistent regarding the effect this variant may have on gene splicing, and in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 c.379+4_379+5delAT was not not observed at a significant allele frequency in large population cohorts (Lek 2016). The nucleotides that are deleted are not conserved across species. Based on currently available information, it is unclear whether BRIP1 c.379+4_379+5delAT is pathogenic or benign. We consider it to be a variant of uncertain significance.
Color RCV000165685 SCV000903213 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-24 criteria provided, single submitter clinical testing

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