rs1800629

Variant names:

• chr6-31575254-G-A
• rs1800629

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	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

GnomAD2 exomes AF: 0.116 AC: 17554 AN: 150892 AF XY: 0.118

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 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 AC: 1151 AN: 9350

Gnomad4 AMR exome AF: 0.0609 AC: 1749 AN: 28742

Gnomad4 ASJ exome AF: 0.0803 AC: 903 AN: 11246

Gnomad4 EAS exome AF: 0.0760 AC: 806 AN: 10602

Gnomad4 SAS exome AF: 0.0760 AC: 4580 AN: 60236

Gnomad4 FIN exome AF: 0.134 AC: 1878 AN: 14012

Gnomad4 NFE exome AF: 0.163 AC: 27754 AN: 169932

Gnomad4 Remaining exome AF: 0.135 AC: 2061 AN: 15316

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 AC: 0.127373 AN: 0.127373

Gnomad4 AMR AF: 0.0870 AC: 0.0870419 AN: 0.0870419

Gnomad4 ASJ AF: 0.0839 AC: 0.0838617 AN: 0.0838617

Gnomad4 EAS AF: 0.0683 AC: 0.068305 AN: 0.068305

Gnomad4 SAS AF: 0.0690 AC: 0.0689655 AN: 0.0689655

Gnomad4 FIN AF: 0.123 AC: 0.122501 AN: 0.122501

Gnomad4 NFE AF: 0.171 AC: 0.170757 AN: 0.170757

Gnomad4 OTH AF: 0.124 AC: 0.124288 AN: 0.124288

Alfa AF: 0.156 Hom.: 6420

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

Feb 09, 2021

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

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

Aug 07, 2021

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

Differences in plasma levels of TNFR2 according to genotypes -

Malaria, cerebral, susceptibility to Other:1

Mar 01, 2006

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Systemic lupus erythematosus, susceptibility to Other:1

Mar 01, 2006

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Inherited susceptibility to asthma Other:1

Mar 01, 2006

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

etanercept response - Efficacy Other:1

Mar 24, 2021

PharmGKB

Significance: drug response

Review Status: reviewed by expert panel

Collection Method: curation

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

Mar 01, 2006

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

MIGRAINE WITHOUT AURA, SUSCEPTIBILITY TO Other:1

Mar 01, 2006

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

SEPTIC SHOCK, SUSCEPTIBILITY TO Other:1

Mar 01, 2006

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

HUMAN IMMUNODEFICIENCY VIRUS DEMENTIA, SUSCEPTIBILITY TO Other:1

Mar 01, 2006

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Endometriosis Other:1

Oct 20, 2021

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

Significance: Affects

Review Status: no assertion criteria provided

Collection Method: case-control

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;