ACE 2 Coding Variants: A Potential X-linked Risk Factor for COVID-19 Disease

William T Gibson; Daniel M Evans; Jianghong An; Steven JM Jones

The range varied from 158,104 X chromosomes genotyped successfully for p.Val488Ala to 183,374 X 127 chromosomes that genotyped successfully for p.Glu35Lys. Variant frequencies in Supplementary Table 128 1 were calculated using the number of alternate allele counts as the numerator and the number of 129 chromosomes genotyped successfully at the locus as the denominator. Aggregating the allele 130 frequencies of ACE2 variants located at the SARS-CoV-2 binding site (i.e. excluding p.Asn720Asp 131 because it is not at the binding site) yields a frequency of 0.0041, which estimates that roughly 3.9 132 . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.05.026633 doi: bioRxiv preprint males per 1000 and 8.5 females per 1000 would harbour a rare allele that might affect the binding of 133 SARS-CoV-2 to cells that express ACE2. Importantly, these rare alleles are not distributed evenly 134 across human subpopulations, as outlined below. 135