ClinVar Miner

Submissions for variant NM_004820.5(CYP7B1):c.850+5G>C

gnomAD frequency: 0.00010  dbSNP: rs202155727
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523484 SCV000621637 uncertain significance not provided 2017-10-25 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CYP7B1 gene. The c.850+5 G>C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.850+5 G>C variant is observed in 33/125006 (0.03%) alleles from individuals of European background, in large population cohorts (Lek et al., 2016). This substitution occurs at a position that is conserved in mammals. However, several in-silico splice prediction models predict that c.850+5 G>C does not impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000818995 SCV000959634 uncertain significance Spastic paraplegia 2022-09-23 criteria provided, single submitter clinical testing This sequence change falls in intron 3 of the CYP7B1 gene. It does not directly change the encoded amino acid sequence of the CYP7B1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs202155727, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CYP7B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 452800). 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 may disrupt the consensus splice site. 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001848918 SCV002104565 uncertain significance Hereditary spastic paraplegia 2019-08-01 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003905317 SCV004725263 likely benign CYP7B1-related disorder 2022-01-25 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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