BRCA1 IVS16+6T-->C is a deleterious mutation that creates an aberrant transcript by activating a cryptic splice donor site.
Results and conclusions are presented that characterize BRCA1 IVS16+6T-->C as a deleterious mutation. BRCA1 transcripts from peripheral blood mononuclear cells of a breast cancer patient with the transition IVS16+6T-->C show the loss of a heterozygous base within codon 871. Additionally, an aberrant RNA splicing product which incorporates 69 bases of the 5' end of intron 16 at the junction of exons 16 and 17 is produced solely from the allele with IVS16+6T-->C. This insertion contains two in-frame stop codons and encodes a protein truncated at residue 1662 (plus 13 residues encoded by the intron). The aberrant transcript is specifically associated with the intronic variant since it was contained within the insertion. Furthermore, sequence analysis of the heterozygous base within codon 871 demonstrates that the two RNA products, productive mRNA and aberrantly spliced RNA, are contributed to exclusively by separate alleles. Finally, the aberrant transcript is produced by the activation of a cryptic splice site which has greater homology with the primate consensus splice sequence than the mutated exon 16 donor site.