ClinVar

Description

The GP1BB p.Ser48Leu variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs536874549) and LOVD 3.0. The variant was identified in control databases in 16 of 164128 chromosomes at a frequency of 0.00009748 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: African in 15 of 12756 chromosomes (freq: 0.001176) and Latino in 1 of 25846 chromosomes (freq: 0.000039), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Other, and South Asian populations. The p.Ser48 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. 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. 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.