ClinVar Miner

Submissions for variant NM_000784.4(CYP27A1):c.435G>T (p.Gly145=)

gnomAD frequency: 0.00001  dbSNP: rs587778796
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center RCV000056114 SCV000267283 likely pathogenic Cholestanol storage disease 2016-03-18 criteria provided, single submitter reference population
Labcorp Genetics (formerly Invitae), Labcorp RCV000056114 SCV000939588 pathogenic Cholestanol storage disease 2024-06-23 criteria provided, single submitter clinical testing This sequence change affects codon 145 of the CYP27A1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CYP27A1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs587778796, gnomAD 0.04%). This variant has been observed in individuals with cerebrotendinous xanthomatosis (PMID: 9521761, 29321515). It has also been observed to segregate with disease in related individuals. This variant is also known as Gly112Gly. ClinVar contains an entry for this variant (Variation ID: 65869). Studies have shown that this variant results in alternative splicing and introduces a premature termination codon (PMID: 9521761). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000056114 SCV001162937 pathogenic Cholestanol storage disease 2024-03-14 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000056114 SCV005647736 likely pathogenic Cholestanol storage disease 2024-05-08 criteria provided, single submitter clinical testing
GeneReviews RCV000056114 SCV000087192 pathologic Cholestanol storage disease 2013-08-01 no assertion criteria provided curation Converted during submission to Pathogenic.
Counsyl RCV000056114 SCV000800527 uncertain significance Cholestanol storage disease 2017-05-09 flagged submission clinical testing
Natera, Inc. RCV000056114 SCV001455782 pathogenic Cholestanol storage disease 2020-09-16 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV003915020 SCV004727954 likely pathogenic CYP27A1-related disorder 2024-02-14 no assertion criteria provided clinical testing The CYP27A1 c.435G>T variant is not predicted to result in an amino acid change (p.=). This variant is predicted to alter splicing based on available splicing prediction programs (SpliceAI, Jaganathan et al. 2019. PubMed ID: 30661751) and a RT-PCR study showed this variant impacts mRNA splicing leading to a cryptic GT Donor site (Figure 5, Chen et al. 1998. PubMed ID: 9521761). This variant has been reported in the homozygous and compound heterozygous states in multiple individuals with cerebrotendinous xanthomatosis (Figure 5, Chen et al. 1998. PubMed ID: 9521761; Figure 2, Tang et al. 2020. PubMed ID: 31914338; Figure 1, Cao et al. 2020. PubMed ID: 33269283). This variant is reported in 0.033% of alleles in individuals of East Asian descent in gnomAD. It has also been described as one of the most common variants observed in Japanese individuals with cerebrotendinous xanthomatosis (Sekijima et al. 2018. PubMed ID: 29321515). This variant is interpreted as likely pathogenic.

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