Table 2. Variants in Qatar, stratified by allele frequency and potential for pathogenicity¹.

Category			Major reference allele (MRA)				Major alternate allele (MAA)
	All variant alleles (GRCh37)		Rare alternate allele (<5% alternate allele frequency)		Common alternate allele (5% to 50% alternate allele frequency)		Common reference allele (50% to 95% alternate allele frequency)		Rare reference allele (95% to 100% alternate allele frequency)		Unobserved reference allele (100% alternate allele frequency)
	n	%	n	%	n	%	n	%	n	%	n	%
All SNPs	20,864,277	100.00	12,948,368	62.06	5,938,490	28.46	1,693,649	8.12	195,466	0.94	88,303	0.42
3–Potentially pathogenic	155,571	0.75	124,947	0.60	23,282	0.11	5,957	0.03	956	<0.01	428	<0.01
2–In gene linked to phenotype	50,757	0.24	40,894	0.20	7,445	0.04	2,002	0.01	290	<0.01	125	<0.01
1–Variant with known link	2,152	0.01	999	<0.01	876	<0.01	253	<0.01	21	<0.01	2	<0.01

The major allele variants are modified in the QTRG genome, such that all reported variants are the minor allele. A total of 230,395 potentially deleterious SNPs in the 917 exomes and 88 genomes were computationally categorized with respect to allele frequency and databases of genes and variants with reported links to a phenotype. Variants were assigned to genes and their function was predicted with respect to ENSEMBL³⁴ gene models using SNPEFF,³² and potentially deleterious coding SNPs (nonsynonymous, splice donor site, splice acceptor site, stop gain, start loss) variants were extracted for further analysis. A database that combines OMIM,³⁵ HGMD,³⁶ GWAS,³⁷ PharmGKB,³⁸ Human Phenotype Ontology³⁹ and ClinVar⁴⁰ was compiled, where these annotations were used to divide the potentially deleterious variants into three categories, variant and gene linked to a phenotype (Category 1), gene but not variant linked to a phenotype (Category 2) and neither variant nor gene linked to a phenotype (Category 3). The totals for each category are shown in the left-most columns, including number and percentage. These variants were then sub-classified into two major (major reference allele, major alternate allele) and five minor categories based on variant allele frequency in Qatar rare alternate allele (up to 5% variant allele frequency), common alternate allele (between 5 and 50% allele frequency), common reference allele (from 50 to 95% alternate allele frequency), rare reference allele (from 95 to 100% alternate allele frequency), unobserved reference allele (100% allele frequency). The major alternate alleles (MAA) are modified in the Qatar Genome (QTRG).

Abbreviation: SNP, single nucleotide polymorphism.