Highly pleiotropic variants mapped onto three fundamental pigmentary genes IRF4, HERC2, TYR; rs12203592, which is an intronic variant in IRF4 gene, was significantly associated with six of the pigmentary traits in our analysis (brown hair, ease sunburn, ease suntan, eye color, freckles, and skin color), and with skin cancer and actinic keratosis. The gene discussed is HERC2; the disease is skin cancer.