rs1800629

chr6-31575254-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.131 in 474,386 control chromosomes in the GnomAD database, including 4,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1582 hom., cov: 31)
  • Exomes 𝑓: 0.13 (3225 hom.)
• Consequence: Unknown
• Clinical Significance: drug response reviewed by expert panel U:2 O:9
• Conservation: PhyloP100: 0.0180

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20989 AN: 152008 Hom.: 1578 Cov.: 31

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.0872

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.0681

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.126

GnomAD3 exomes AF: 0.116 AC: 17554 AN: 150892 Hom.: 1279 AF XY: 0.118 AC XY: 9726 AN XY: 82290

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.0594

Gnomad ASJ exome AF: 0.0762

Gnomad EAS exome AF: 0.0896

Gnomad SAS exome AF: 0.0760

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.124

GnomAD4 exome AF: 0.128 AC: 41363 AN: 322260 Hom.: 3225 Cov.: 0 AF XY: 0.125 AC XY: 22845 AN XY: 183234

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.0609

Gnomad4 ASJ exome AF: 0.0803

Gnomad4 EAS exome AF: 0.0760

Gnomad4 SAS exome AF: 0.0760

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.138 AC: 20992 AN: 152126 Hom.: 1582 Cov.: 31 AF XY: 0.132 AC XY: 9824 AN XY: 74368

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0870

Gnomad4 ASJ AF: 0.0839

Gnomad4 EAS AF: 0.0683

Gnomad4 SAS AF: 0.0690

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.124

Alfa AF: 0.152 Hom.: 3251

Bravo AF: 0.135

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Significance: drug response

Submissions summary: Uncertain:2 Other:9

Revision: reviewed by expert panel

Submissions by phenotype

Susceptibility to severe coronavirus disease (COVID-19) Uncertain:1

Uncertain significance, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Feb 09, 2021

- -

Susceptibility to severe coronavirus disease (COVID-19) due to high plasma levels of TNF, TNFR, and/or TNFR4 Uncertain:1

Uncertain significance, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Aug 07, 2021

Differences in plasma levels of TNFR2 according to genotypes -

Malaria, cerebral, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2006

- -

Human immunodeficiency virus dementia, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2006

- -

Septic shock, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2006

- -

Systemic lupus erythematosus, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2006

- -

Migraine without aura, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2006

- -

Inherited susceptibility to asthma Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2006

- -

etanercept response - Efficacy Other:1

drug response, reviewed by expert panel

curation

PharmGKB

Mar 24, 2021

PharmGKB Level of Evidence 2B: Variants in Level 2B clinical annotations are not in PharmGKB’s Tier 1 VIPs. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2B clinical annotations must be supported by at least two independent publications. Drug-variant association: Efficacy

Psoriatic arthritis, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2006

- -

Endometriosis Other:1

Affects, no assertion criteria provided

case-control

Laboratorio de Investigación del Departamento de Salud, Universidad Iberoamericana A.C.

Oct 20, 2021

Mexican mestizo women with severe stage of endometriosis have higher frequencies of TNF*2-, IL1B*2- and IL1RN*2-alleles, which may explain a possible correlation with disease severity rather than predisposition or risk. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.9
Dann	Benign	0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1800629; hg19: chr6-31543031;