ClinVar Miner

Submissions for variant NM_173483.4(CYP4F22):c.712G>A (p.Ala238Thr)

gnomAD frequency: 0.00003  dbSNP: rs572278771
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000912869 SCV001057994 likely benign not provided 2024-01-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002298734 SCV002599029 likely benign not specified 2022-09-03 criteria provided, single submitter clinical testing Variant summary: CYP4F22 c.712G>A (p.Ala238Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00078 in 251372 control chromosomes (gnomAD), predominantly at a frequency of 0.0062 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 9 fold of the estimated maximal expected allele frequency for a pathogenic variant in CYP4F22 causing Lamellar Ichthyosis (0.00071), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. c.712G>A has been reported in the literature in individuals affected with Congenital Ichthyosis (Scott_2013, Hotz_2018), however these reports do not provide unequivocal conclusions about association of the variant with disease. When assayed for -hydroxylase activity in a cell-based assay, the variant was found to have comparable activity as WT (Nohara_2021). Three ClinVar submitters have assessed the variant since 2014 without evidence for independent evaluation: one classified the variant as pathogenic, one as uncertain significance, and one as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Institute for Human Genetics, University Medical Center Freiburg RCV000678431 SCV000804505 pathogenic Autosomal recessive congenital ichthyosis 5 2018-04-23 no assertion criteria provided clinical testing
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City RCV000678431 SCV000854736 uncertain significance Autosomal recessive congenital ichthyosis 5 2018-07-31 no assertion criteria provided clinical testing

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