Table 1.

Predicted effect of SNP 1476G/A on affinity score for binding of SR protein

  • Predicted effect of SNP rs1800860 on the affinity score for binding of RET mRNA to core spliceosome components. We used ESEfinder software to predict the effect of an adenosine versus guanine nucleotides at position 1476 of the human RET transcript on binding to two core protein components of the spliceosome (SF2/ASF and SC35). The matrix score for SF2/ASF is reduced from 3.08 for the ancestral CAGGCGT sequence to 0.50 for the less common CAGGCAT variant (threshold for normal splicing efficiency = 1.96). Similarly, affinity for the SC35 component is reduced from 3.85 to 2.10 (threshold = 2.40). Based on these predictions, we hypothesized that the rs1800860 A allele (1476A) might lead to aberrant RET mRNA splicing.