Schema for Rare Harmful Vars - Rare variants underlying COVID-19 severity and susceptibility from the COVID Human Genetics Effort
  Database: hg19    Primary Table: covidMuts Data last updated: 2020-10-30
Big Bed File: /gbdb/hg19/covidMuts/covidMuts.bb
Item Count: 23
Format description: Browser extensible data (12 fields) plus two sequences
fieldexampledescription
chromchr11Chromosome (or contig, scaffold, etc.)
chromStart613332Start position in chromosome
chromEnd614301End position in chromosome
nameT>C & C>TName of item
score0Score from 0-1000
strand.+ or -
thickStart613332Start of where display should be thick (start codon)
thickEnd614301End of where display should be thick (stop codon)
reserved0,0,0Used as itemRgb as of 2004-11-22
blockCount2Number of blocks
blockSizes1,1Comma separated list of block sizes
chromStarts0,968Start positions relative to chromStart
refCReference Allele
altTAlternate Allele
rsId.If in dbSNP: rs-ID
zygocompound hetZygosity
geneIRF7Gene
genotypeg.613333:T>C and g.614843:C>T (p.Met371Val/p.Asp117Asn and p.Met371Val/p.Asp117Asn)Genotype
inhModeARInheritance Mode

Sample Rows
 
chromchromStartchromEndnamescorestrandthickStartthickEndreservedblockCountblockSizeschromStartsrefaltrsIdzygogenegenotypeinhMode
chr11613332614301T>C & C>T0.6133326143010,0,021,10,968CT.compound hetIRF7g.613333:T>C and g.614843:C>T (p.Met371Val/p.Asp117Asn and p.Met371Val/p.Asp117Asn)AR
chr11613337613338C>T0.6133376133380,0,0110CTrs765147452hetIRF7p.Arg369Gln/WTAD
chr11613353613354G>GC0.6133536133540,0,0110GGCrs970393690homIRF7p.Pro364fs/p.Pro364fsAR
chr11613966613980CGGGCTGGGGCCCG>C0.6139666139800,0,01140CGGGCTGGGGCCCGCrs753582183hetIRF7p.Pro246fs/WTAD
chr11614300614301G>A0.6143006143010,0,0110GArs756347258hetIRF7p.Gln185*/WTAD
chr11614907614908A>G0.6149076149080,0,0110AG.hetIRF7p.Phe95Ser/WTAD
chr11615095615096A>C0.6150956150960,0,0110AC.hetIRF7p.Arg7fs/WTAD
chr116777059867770599C>A0.67770598677705990,0,0110CA.hetUNC93B1p.Glu96*/WTAD

Rare Harmful Vars (covidMuts) Track Description
 

Description

This track shows rare variants associated with monogenic congenital defects of immunity to the SARS-CoV-2 virus identified by the COVID Human Genetic Effort. This international consortium aims to discover truly causative variations: those underlying severe forms of COVID-19 in previously healthy individuals, and those that make certain individuals resistant to infection by the SARS-CoV2 virus despite repeated exposure.

The major feature of the small set of variants in this track is that they are functionally tested to be deleterious and genetically tested to be disease-causing. Specifically, rare variants were predicted to be loss-of-function at human loci known to govern interferon (IFN) immunity to influenza virus in patients with life-threatening COVID-19 pneumonia, relative to subjects with asymptomatic or benign infection. These genetic defects display incomplete penetrance for influenza respiratory distress and only appear clinically upon infection with the more virulent SARS-CoV-2.

Display Conventions

Only eight genes with 23 variants are contained in this track. Use the links below to navigate to the gene of interest or view all eight genes together using the following sessions for hg38 or hg19.

Gene Name Human GRCh37/hg19 Assembly Human GRCh38/hg38 Assembly
TLR3 chr4:186990309-187006252 chr4:186069152-186088069
IRF7 chr11:612555-615999 chr11:612591-615970
UNC93B1 chr11:67758575-67771593 chr11:67991100-68004097
TBK1 chr12:64845840-64895899 chr12:64452120-64502114
TICAM1 chr19:4815936-4831754 chr19:4815932-4831704
IRF3 chr19:50162826-50169132 chr19:49659570-49665875
IFNAR1 chr21:34697214-34732128 chr21:33324970-33359864
IFNAR2 chr21:34602231-34636820 chr21:33229974-33264525

Methods

This track uses variant calls in autosomal IFN-related genes from whole exome and genome data with a MAF lower than 0.001 (gnomAD v2.1.1) and experimental demonstration of loss-of-function. The patient population studied consisted of 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection of varying ethnicities. Variants underlying autosomal-recessive or autosomal-dominant deficiencies were identified in 23 patients (3.5%) 17 to 77 years of age. The proportion of individuals carrying at least one variant was compared between severe cases and control cases by means of logistic regression with the likelihood ratio test. Principal Component Analysis (PCA) was conducted with Plink v1.9 software on whole exome and genome sequencing data with the 1000 Genomes (1kG) Project phase 3 public database as reference. Analysis of enrichment in rare synonymous variants of the genes was performed to check the calibration of the burden test. The odds ratio was also estimated by logistic regression and adjusted for ethnic heterogeneity.

Data Access

The raw data can be explored interactively with the Table Browser, or the Data Integrator. Please refer to our mailing list archives for questions, or our Data Access FAQ for more information.

Credits

Thanks to the COVID Human Genetic Effort contributors for making these data available, and in particular to Qian Zhang at the Rockefeller University for review and input during browser track development.

References

Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, Ogishi M, Sabli IKD, Hodeib S, Korol C et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science. 2020 Sep 24;. PMID: 32972995