Scoring variants in an exome to predict an effect of the variants on gene function

A system for scoring variants in an exome to predict an effect of the variants on gene function, the system comprising:

• a memory storing instructions;
• one or more communication interfaces;
• and
• one or more hardware processors coupled to the memory via the one or more communication interfaces, wherein the one or more hardware processors are configured by the instructions to:
• receive a dataset comprising a plurality of variants corresponding to the exome, wherein the plurality of variants are one or more single nucleotide variants (SNVs) and one or more indels;
• annotate each of the plurality of variants comprised in the dataset with corresponding variant information, to form a plurality of annotated variants;
• identify one or more variants, out of the plurality of annotated variants, occurring in a transcript of a plurality of transcripts corresponding to a protein coding gene comprised in the exome, to form a set of variants, wherein the one or more variants are identified based on a corresponding transcript ID;
• separate variants in a Y-chromosome from the set of variants, to form a revised set of variants;
• identify (i) one or more SNVs present in the coding exonic region and a coding intronic region, and one or more indels present in the coding intronic region, based on a corresponding minor allele frequency (MAF) value, and (ii) one or more indels present in a coding exonic region, from the revised set of variants, to form a subset of variants;
• assess the identified one or more SNVs and the identified one or more indels from the subset of variants, wherein assessing the identified one or more SNVs comprises (i) selecting the one or more SNVs based on a corresponding ethnicity wise allele frequency (ETH_AF) value, from the identified one or more SNVs, and (ii) assigning a score for each of the selected one or more SNVs, based on (i) presence in the coding exonic region and (ii) presence in the coding intronic region, and wherein assessing the identified one or more indels comprises assigning the score for each of the identified one or more indels, based on (i) presence in a coding exonic intronic boundary region (ii) presence in the coding exonic region, and (iii) presence in the coding intronic region;
• assign a final score for each of the selected one or more SNVs and the identified one or more indels, based on the corresponding assigned score, a corresponding genomic evolutionary rate profiling (Gerp)++ RSbase value and a corresponding sub-region residual variation intolerance scores (SubRVIS) value;
• and
• predict the effect of the one or more variants on the gene function, based on the corresponding final score, corresponding genotype information and haploinsufficiency of the gene.

A computer program product comprising a non-transitory computer readable medium having a computer readable program embodied therein, wherein the computer readable program, when executed on a computing device, causes the computing device to:

• receive a dataset comprising a plurality of variants corresponding to the exome, wherein the plurality of variants are one or more single nucleotide variants (SNVs) and one or more indels;
• annotate each of the plurality of variants comprised in the dataset with corresponding variant information, to form a plurality of annotated variants;
• identify one or more variants, out of the plurality of annotated variants, occurring in a transcript of a plurality of transcripts corresponding to a protein coding gene comprised in the exome, to form a set of variants, wherein the one or more variants are identified based on a corresponding transcript ID;
• separate variants in a Y-chromosome from the set of variants, to form a revised set of variants;
• identify (i) one or more SNVs present in the coding exonic region and a coding intronic region, and one or more indels present in the coding intronic region, based on a corresponding minor allele frequency (MAF) value, and (ii) one or more indels present in a coding exonic region, from the revised set of variants, to form a subset of variants;
• assess the identified one or more SNVs and the identified one or more indels from the subset of variants, wherein assessing the identified one or more SNVs comprises (i) selecting the one or more SNVs based on a corresponding ethnicity wise allele frequency (ETH_AF) value, from the identified one or more SNVs, and (ii) assigning a score for each of the selected one or more SNVs, based on (i) presence in the coding exonic region and (ii) presence in the coding intronic region, and wherein assessing the identified one or more indels comprises assigning the score for each of the identified one or more indels, based on (i) presence in a coding exonic intronic boundary region (ii) presence in the coding exonic region, and (iii) presence in the coding intronic region;
• assign a final score for each of the selected one or more SNVs and the identified one or more indels, based on the corresponding assigned score, a corresponding genomic evolutionary rate profiling (Gerp)++ RSbase value and a corresponding sub-region residual variation intolerance scores (SubRVIS) value;
• and
• predict the effect of the one or more variants on the gene function, based on the corresponding final score, corresponding genotype information and haploinsufficiency of the gene.