This work focuses on identifying oncogenic variants through long-read RNA-seq (lrRNA-seq) and understanding how RNA processing influences the functional impact of these variants. We developed FLAIR3, an enhanced version of FLAIR (Full-Length Alternative Isoform Analysis of RNA), which performs an integrated analysis of SNVs, gene fusions, and alternative splicing using lrRNA-seq and predicts functional changes to the amino acid sequence. We performed ONT lrRNA-seq on three osteosarcoma cell lines and PacBio lrRNA-seq on paired normal and tumor tissue from two lung adenocarcinomas. We then used FLAIR3 to identify potential cancer driver variants and to determine how splicing modulates their expression and function. In the osteosarcoma samples, FLAIR3 revealed alternative splicing of amplified drivers as well as gene fusions in oncogenic genes with alternative splicing. In the lung adenocarcinoma samples, FLAIR3 revealed tumor-specific damaging SNVs and alternative splicing in oncogenic genes, specifically BRAF, CDKN2A, and TP53. These findings reveal the prevalence of alternative splicing of oncogenic variant-containing transcripts and could lead to improved precision medicine.