Clinical variant classification. (A) Variants assayed with assigned clinical significance in ClinVar (n = 64) including pathogenic/likely pathogenic (P/LP), conflicting classifications of pathogenicity, uncertain significance (VUS), and benign/likely benign (B/LB). Nonsense and missense variants were excluded. (B) Estimation of likelihood ratio for pathogenicity for each splicing impact category based on 10 P/LP and 18 B/LB control variants from ClinVar. (C) Synonymous and intronic variants (n = 90) that resulted in low/no FL reduction can be assigned with BP7_Strong (RNA) code under the ACMG/AMP framework of variant classification (Walker et al. 2023).