ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.1608+4G>T

dbSNP: rs878853974
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230595 SCV000284782 uncertain significance Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 2023-07-14 criteria provided, single submitter clinical testing This sequence change falls in intron 5 of the CASR gene. It does not directly change the encoded amino acid sequence of the CASR protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CASR-related conditions. ClinVar contains an entry for this variant (Variation ID: 237757). 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. 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 RCV003165603 SCV003858287 uncertain significance Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis 2023-01-23 criteria provided, single submitter clinical testing The c.1608+4G>T intronic variant results from a G to T substitution 4 nucleotides after coding exon 4 in the CASR gene. This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003977646 SCV004793453 likely benign CASR-related condition 2021-11-03 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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