Table 1.

Overview of the top exonic variants prioritized in the studied CRC family

Gene name	Chromosomal position	Exonic classification	Pedigree segregation	NFE allele frequency		CADD SCORE	Conservational scores			Intolerance scores (%)	Deleteriousness scoresa (%)	Amino acid change	Snap2		Protein function
				ExAC	gnomAD		GERP +  +	PhyloP	PhastCons				Effect score	Accuracy (%)
PTGES	9_132501952_C_T	Nonsyn SNV	III2, III3, III4, III5, IV2	2.10 × 10–4	8.43 × 10–5	34	4.67	7.723	1	75	80	A133T	16	59	Glutathione-dependent prostaglandin E synthase, involved in inflammatory responses, fever, pain
SLC15A4	12_129285482_T_C	Nonsyn SNV	III2, III3, III4, III5, IV2	0	0	23.7	5.49	5.609	1	100	90	Y444C	44	71	Proton-dependent peptide/histidine transporter, regulation of innate immune responses

Chromosomal position, classification, pedigree segregation, allele frequency in the Non-Finnish European (NFE) population, PHRED-like CADD score, conservational score and the percentage of reached intolerance and deleteriousness scores are summarized for each variant. Snap² results for the predicted amino acid changes are included with calculated effect scores and accuracies given in %. Respective protein functions of the encoded gene products are derived from Genecards (Stelzer et al. 2016). Non-syn SNV-non-synonymous single nucleotide variant

^aFollowing predictions given by deleteriousness scores were considered as favorable in our analysis: SIFT–Damaging (D); Polyphen2_HumDiv, Polyphen2_HumVar–Probably damaging (D) and Possibly damaging (P); LRT–Deleterious (D); MutationTaster–Disease causing (D) and disease causing automatic (A); MutationAssesor–High (H) and medium (M); FATHMM–Damaging (D); MetaSVM–Damaging (D); MetaLR–Damaging (D); Reliability Index ≥ 5; VEST3 ≥ 0.5; PROVEAN–Damaging (D)