ClinVar Miner

Submissions for variant NM_001139.3(ALOX12B):c.1463G>A (p.Arg488His)

gnomAD frequency: 0.00001  dbSNP: rs763468558
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002222692 SCV002500470 pathogenic Lamellar ichthyosis 2022-03-18 criteria provided, single submitter clinical testing Variant summary: ALOX12B c.1463G>A (p.Arg488His) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251322 control chromosomes (gnomAD). c.1463G>A has been reported in the literature in multiple individuals affected with autosomal recessive congenital ichthyoses, including several homozygotes (Eckl_2005, Seidl-Philipp_2020) and at least one compound heterozygote (Israeli_2013). These data indicate that the variant is very likely to be associated with disease. Eckl et al (2005) also examined the variant protein's ability to convert arachidonic acid and determined that the variant protein had complete loss of enzymatic activity. One ClinVar submitter has assessed the variant since 2014: the variant was classified as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
PreventionGenetics, part of Exact Sciences RCV003405498 SCV004109813 pathogenic ALOX12B-related disorder 2023-01-31 criteria provided, single submitter clinical testing The ALOX12B c.1463G>A variant is predicted to result in the amino acid substitution p.Arg488His. This variant has been previously reported in the homozygous or compound heterozygous state in individuals with autosomal recessive congenital ichthyosis (Eckl et al. 2005. PubMed ID: 16116617; Ashoor et al. 2006. PubMed ID: 16792775; Figure 2A, Hotz et al. 2021. PubMed ID: 33435499; Saat et al. 2022. PubMed ID: 35734965; Israeli et al. 2013. PubMed ID: 23621129). This variant is reported in 0.0050% of alleles in individuals of East Asian descent in gnomAD ( This variant is interpreted as pathogenic.
Institute for Human Genetics, University Medical Center Freiburg RCV001289523 SCV001477397 pathogenic Autosomal recessive congenital ichthyosis 2 2021-01-07 no assertion criteria provided clinical testing

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