Description
The CYP27A1 p.Arg479Gly variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs72551322) as “With Pathogenic allele”. The variant was identified in ClinVar with conflicting interpretations of pathogenicity, with submissions of likely pathogenic (Counsyl), pathogenic (OMIM and GeneReviews), and uncertain significance (EGL Genetics Diagnostics). The associated condition is cholesterol storage disease. The variant was identified in control databases in 4 of 282188 chromosomes at a frequency of 0.000014 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Latino in 1 of 35424 chromosomes (freq: 0.000028) and European (non-Finnish) in 3 of 128792 chromosomes (freq: 0.000023); it was not observed in the African, Ashkenazi Jewish, East Asian, European (Finnish), Other, and South Asian populations. This variant was identified as a causal homozygous variant in a patient with Cerebrotendinous xanthomatosis and was identified in another case study in the compound heterozygous state in a patient with unusual Cerebrotendinous xanthomatosis with fronto-temporal dementia (Di Taranto_2016_PMID:27225395; Guyant-Marechal_2005_PMID:16278884). The variant occurs outside of the splicing consensus sequence and four out of four in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, and GeneSplicer) do not predict a greater than 10% difference in splicing. The p.Arg479 residue is conserved in mammals but not more distantly related organisms and four out of five computational analyses (PolyPhen-2, SIFT, BLOSUM, and MutationTaster) suggest that the variant may impact the protein. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | unknown | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
