ClinVar

Description

The CTHRC1 p.Arg142His variant was not identified in the literature nor was it identified in ClinVar, Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs145062750) and was found in control databases in 113 of 282640 chromosomes at a frequency of 0.0004 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 87 of 24968 chromosomes (freq: 0.003484), South Asian in 18 of 30612 chromosomes (freq: 0.000588), Other in 1 of 7218 chromosomes (freq: 0.000139), Latino in 2 of 35436 chromosomes (freq: 0.000056), East Asian in 1 of 19952 chromosomes (freq: 0.00005) and European (non-Finnish) in 4 of 128968 chromosomes (freq: 0.000031), while the variant was not observed in the Ashkenazi Jewish and European (Finnish) populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Arg142 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.