ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1A>G (p.Met1Val) (rs764585550)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167101 SCV000217931 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000167101 SCV000904226 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-29 criteria provided, single submitter clinical testing
Counsyl RCV000410570 SCV000490065 uncertain significance Fanconi anemia, complementation group J 2016-10-27 criteria provided, single submitter clinical testing
Counsyl RCV000411221 SCV000490066 uncertain significance Neoplasm of ovary 2016-10-27 criteria provided, single submitter clinical testing
GeneDx RCV000484413 SCV000571262 uncertain significance not provided 2017-01-17 criteria provided, single submitter clinical testing The c.1A>G variant in the BRIP1 gene alters the initiator Methionine codon and the resultant protein would be described as "p.Met1?" to signify that it is not known if the loss of Met1 prevents all protein translation or if an abnormal protein is produced using an alternate Methionine codon. There are alternate in-frame Methionine residues at codons 4, 28, and 29 which have the potential to be used to initiate protein translation. BRIP1 c.1A>G has not, to our knowledge, been published in the literature as pathogenic or benign. This variant was not observed at a significant allele frequency in large population cohorts (Lek 2016). Based on currently available evidence, it is unclear whether BRIP1 c.1A>G is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000474167 SCV000547365 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-09-05 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the BRIP1 mRNA (c.1A>G). While it is expected to result in an absent or disrupted protein product, alternate in-frame methionines at codons 4, 28, or 29, located downstream of the initiator codon could potentially rescue the translation initiation. However, functional studies have not been done to test whether these alternate methionines are utilized. This variant is present in population databases (rs764585550, 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: 187378). 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.

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