TP53 and cancer: The observed mutations—all deletions significantly larger than expected (Fig. 3b) (median length = 17 bp versus 1 bp expected; P = 7.4 × 10−4, one-sided Mann–Whitney U-test)—specifically affected exon 1 of the canonical 5′ untranslated region (UTR), disrupted critical sequence elements (transcription start site, WRAP53 binding sequence46, internal ribosome entry site47,48 and the donor splice region of the multi-exonic 5′ UTR) (Fig. 3a) and exhibited enrichment comparable to cryptic exonic splice SNVs in TP53, which are well-characterized cancer drivers49 (Fig. 3c).