NM_000527.5(LDLR):c.1846-10G>T variant is classified as Likely benign for Familial Hypercholesterolemia by applying evidence codes (PM2, BP2 and BP4) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). The supporting evidence is as follows: PM2 - PopMax MAF = 0.00009643 (0.0096%) in Ashkenazi Jewish exomes+genomes (gnomAD v2.1.1). BP2 - Variant identified in an index case with heterozygous FH phenotype (LDLc = 6.5 mmol/l) and APOB variant p.(Arg3527Gln), classified as Pathogenic by the general ACMG guidelines from Robarts Research Institute. BP4 - No REVEL available, splicing evaluation needed. Functional data on splicing not available. A) variant is located at -20 to +3 bases of canonical acceptor splicing site MES scores: de novo acceptor = 11.36, authentic acceptor = 9.58. Ratio variant/wt = 1.18. It is above 1.0. B) The variant is located within range but does not create de novo GT site. C) Variant not on limits. Variant is not predicted to alter splicing. So BP4 is met. Variant has 2 BP evidence codes towards Benign, enough to classify as Likely benign, and only 1 PM evidence code towards Pathogenic. The Benign criteria overwhelms the Pathogenic criteria, so we are confident in classifying this variant as Likely benign.