SNP annotation

[1] Single nucleotide polymorphisms (SNPs) play an important role in genome wide association studies because they act as primary biomarkers.

[6] Many annotation algorithms focus on single nucleotide variants (SNVs), considered more rare than SNPs as defined by their minor allele frequency (MAF).

[citation needed] As a consequence, training data for the corresponding prediction methods may be different and hence one should be careful to select the appropriate tool for a specific purpose.

In this type of annotation more emphasis is given to genetic variation that disrupts the protein function domain, protein-protein interaction and biological pathway.

The function of non-coding variants are extensive in terms of the affected genomic region and they involve in almost all processes of gene regulation from transcriptional to post translational level [11] Transcriptional gene regulation process depends on many spatial and temporal factors in the nucleus such as global or local chromatin states, nucleosome positioning, TF binding, enhancer/promoter activities.

Distinctive structural features are required for many RNA molecules and cis-acting regulatory elements to execute effective functions during gene regulation.

Classical bioinformatics tools, such as SIFT, Polyphen and MutationTaster, successfully predict the functional consequence of non-synonymous substitution.

[16][17][18][19] PopViz webserver provides a gene-centric approach to visualize the mutation damage prediction scores (CADD, SIFT, PolyPhen-2) or the population genetics (minor allele frequency) versus the amino acid positions of all coding variants of a certain human gene.

[20] Comparative genomics approaches were used to predict the function-relevant variants under the assumption that the functional genetic locus should be conserved across different species at an extensive phylogenetic distance.

Functional prediction of variants’ effect in different biological processes is pivotal to pinpoint the molecular mechanism of diseases/traits and direct the experimental validation.

Some of the available SNPs annotation tools are as follows SNPeff, Ensembl Variant Effect Predictor (VEP), ANNOVAR, FATHMM, PhD-SNP, PolyPhen-2, SuSPect, F-SNP, AnnTools, SeattleSeq, SNPit, SCAN, Snap, SNPs&GO, LS-SNP, Snat, TREAT, TRAMS, Maviant, MutationTaster, SNPdat, Snpranker, NGS – SNP, SVA, VARIANT, SIFT, LIST-S2, PhD-SNP and FAST-SNP.

[52] Simultaneous use of multiple, varied functional annotations could improve rare variants association analysis power of whole exome and whole genome sequencing studies.

[53] Some tools have been developed to enable functionally-informed phenotype-genotype association analysis for common and rare variants by incorporating functional annotations in biobank-scale cohorts.

From a user's point of view, it is more efficient to submit a set of SNPs and receive results in a single step, which makes meta-servers the most attractive choice.