ClinVar Miner

Submissions for variant NM_000784.4(CYP27A1):c.844+1G>A

dbSNP: rs397515354
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000004479 SCV000797972 pathogenic Cholestanol storage disease 2018-02-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000004479 SCV001220276 pathogenic Cholestanol storage disease 2024-01-25 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the CYP27A1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs397515354, gnomAD 0.002%). Disruption of this splice site has been observed in individual(s) with cerebrotendinous xanthomatosis (PMID: 8514861, 9254865, 10430841). It has also been observed to segregate with disease in related individuals. This variant is also known as 865+1G>A. ClinVar contains an entry for this variant (Variation ID: 4257). Studies have shown that disruption of this splice site results in skipping of exon 4, but is expected to preserve the integrity of the reading-frame (PMID: 9254865). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001268682 SCV001447795 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
GeneDx RCV001268682 SCV005201737 pathogenic not provided 2023-09-18 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect (skipping of exon 4 and leading to a loss of 198bp in the mRNA and of 66 amino acids in the enzyme molecule) (PMID: 9254865); Not observed at significant frequency in large population cohorts (gnomAD); Also known as c.865+1G>A; This variant is associated with the following publications: (PMID: 25525159, 31589614, 20301583, 10430841, 27678445, 9254865)
OMIM RCV000004479 SCV000024652 pathogenic Cholestanol storage disease 1993-06-01 no assertion criteria provided literature only
GeneReviews RCV000004479 SCV000087232 pathologic Cholestanol storage disease 2013-08-01 no assertion criteria provided curation Converted during submission to Pathogenic.
Natera, Inc. RCV000004479 SCV002078785 pathogenic Cholestanol storage disease 2017-09-26 no assertion criteria provided clinical testing

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