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Fig. 5 | Genome Biology

Fig. 5

From: Introme accurately predicts the impact of coding and noncoding variants on gene splicing, with clinical applications

Fig. 5

Introme performance in clinical applications. A The Introme scores and the functional scores calculated for BRCA1 variants assessed using a saturation mutagenesis screen [27]. Variants with functional scores >  − 0.748 are classified as tolerated whilst functional scores <  =  − 1.328 correspond to non-functional variants, as determined in the original study [27]. Variants are coloured by their ClinVar pathogenicity classifications (P: pathogenic; LP: likely pathogenic; VUS: variant of uncertain significance; B: benign; LB: likely benign). B Introme scores of variants tested for splice-altering impacts by RT-PCR in a diagnostic lab. Variants were classed as ‘assay failed’ if the RT-PCR validation was not able to be performed on the sample. C–E Lollipop plot of the splice-altering variants identified by Introme in the ZERO childhood cancer cohort [28] for genes C NF1, D ATM, and E RB1, made using ProteinPaint [29]. Each circle represents the location of at least one genetic variant identified as reportable and splice-altering in the ZERO cohort (red: somatic variant, blue: germline variant). Shaded areas on the transcript represent protein domains. F–H Splice-altering variants in PKD1 identified using Introme in patients with polycystic kidney disease. RT-PCR was performed using patient (P) and control (C) samples, with the corresponding transcripts numbered and represented above the gels. Asterisks mark the location of the variants in the diagram. The variants are F PKD1:c.7489 + 5G > A, G PKD1:c.11014-10C > A, and H PKD1:c.10167 + 25_10167 + 43del19. I A violin plot showing Introme scores for 7200 randomly selected variants with different population allele frequencies. In A, B, and I, the horizontal dashed line is the default Introme score threshold of 0.61

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