RB1 and cancer: For the validation, we performed Sanger sequencing for the 20 variants on 14 selected genes, i.e., five genes harboring frequent ICC mutations (KRAS, TP53, APC, IDH1, and PTPN3), six cancer-related genes in TARGET database (RB1, MAP2K1, MED12, NF1, RAF1, and XPO1) and selected genes in the remaining categories (BAP1, ROBO1 and SMAD7) (Supplementary Figure S1).