ClinVar

Description

A variant of uncertain significance has been identified in the CYP7B1 gene. The R486S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. However, a missense variant at the same position (R486C) has been has been previously reported in the homozygous and compound heterozygous state in several individuals with spastic paraplegia (Goizet et al., 2009; Schlipf et al., 2011). The R486S variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. The R486S variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.