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NM_000594.3(TNF):c.-488G>A

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Interpretation:
drug response​

Review status:
reviewed by expert panel
Submissions:
11
First in ClinVar:
May 22, 2016
Most recent Submission:
Jun 18, 2022
Last evaluated:
Mar 24, 2021
Accession:
VCV000225964.9
Variation ID:
225964
Description:
single nucleotide variant
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NM_000594.3(TNF):c.-488G>A

Allele ID
227757
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
6p21.33
Genomic location
6: 31575254 (GRCh38) GRCh38 UCSC
6: 31543031 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000006.12:g.31575254G>A
NC_000006.11:g.31543031G>A
NG_007462.1:g.4682G>A
NG_012010.1:g.8156G>A
Protein change
-
Other names
-308G-A
Canonical SPDI
NC_000006.12:31575253:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
0.09026 (A)

Allele frequency
1000 Genomes Project 0.09026
The Genome Aggregation Database (gnomAD), exomes 0.11634
Trans-Omics for Precision Medicine (TOPMed) 0.13494
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.14142
The Genome Aggregation Database (gnomAD) 0.14163
Trans-Omics for Precision Medicine (TOPMed) 0.14314
The Genome Aggregation Database (gnomAD) 0.14683
Exome Aggregation Consortium (ExAC) 0.16159
Links
PharmGKB Clinical Annotation: 655384799
ClinGen: CA3713873
OMIM: 191160.0004
dbSNP: rs1800629
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
drug response 1 reviewed by expert panel Mar 24, 2021 RCV000211242.4
Susceptibility to severe coronavirus disease (COVID-19)
Uncertain significance 1 no assertion criteria provided Feb 9, 2021 RCV001354056.2
Migraine without aura, susceptibility to
risk factor 1 no assertion criteria provided Mar 1, 2006 RCV001807639.2
risk factor 1 no assertion criteria provided Mar 1, 2006 RCV001807634.2
risk factor 1 no assertion criteria provided Mar 1, 2006 RCV001807635.2
Susceptibility to severe coronavirus disease (COVID-19) due to high plasma levels of TNF, TNFR, and/or TNFR4
Uncertain significance 1 no assertion criteria provided Aug 7, 2021 RCV001836755.2
risk factor 1 no assertion criteria provided Mar 1, 2006 RCV001807636.2
Septic shock, susceptibility to
risk factor 1 no assertion criteria provided Mar 1, 2006 RCV001807637.2
Affects 1 no assertion criteria provided Oct 20, 2021 RCV001824024.2
Human immunodeficiency virus dementia, susceptibility to
risk factor 1 no assertion criteria provided Mar 1, 2006 RCV001807638.2
risk factor 1 no assertion criteria provided Mar 1, 2006 RCV001807640.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
TNF - - GRCh38
GRCh38
GRCh38
GRCh38
GRCh38
GRCh38
GRCh38
GRCh38
GRCh37
14 25

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter More information
drug response
(Mar 24, 2021)
reviewed by expert panel
Method: curation
etanercept response - Efficacy
Drug used for Arthritis, Psoriatic , Arthritis, Rheumatoid , Crohn Disease , Inflammation , Psoriasis , and Spondylitis, Ankylosing
Affected status: yes
Allele origin: germline
PharmGKB
Accession: SCV000268228.4
First in ClinVar: May 22, 2016
Last updated: Jun 18, 2022
Comment:
Drug is not necessarily used to treat response condition
Publications:
PubMed (7)
Other databases
https://www.pharmgkb.org/variant… https://www.pharmgkb.org/variant/PA166156997
https://www.pharmgkb.org/clinica… https://www.pharmgkb.org/clinicalAnnotation/655384799
Comment:
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 … (more)
risk factor
(Mar 01, 2006)
no assertion criteria provided
Method: literature only
PSORIATIC ARTHRITIS, SUSCEPTIBILITY TO
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000033440.2
First in ClinVar: Apr 04, 2013
Last updated: Sep 09, 2016
Publications:
PubMed (13)
Comment on evidence:
Mira et al. (1999) referred to the TNFA promoter polymorphisms at position -308 as TNF1 for guanine and TNF2 for adenine. In a multicenter study … (more)
risk factor
(Mar 01, 2006)
no assertion criteria provided
Method: literature only
SYSTEMIC LUPUS ERYTHEMATOSUS, SUSCEPTIBILITY TO
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000033441.2
First in ClinVar: Apr 04, 2013
Last updated: Sep 09, 2016
Publications:
PubMed (13)
Comment on evidence:
Mira et al. (1999) referred to the TNFA promoter polymorphisms at position -308 as TNF1 for guanine and TNF2 for adenine. In a multicenter study … (more)
risk factor
(Mar 01, 2006)
no assertion criteria provided
Method: literature only
MALARIA, CEREBRAL, SUSCEPTIBILITY TO
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000033442.2
First in ClinVar: Apr 04, 2013
Last updated: Sep 09, 2016
Publications:
PubMed (13)
Comment on evidence:
Mira et al. (1999) referred to the TNFA promoter polymorphisms at position -308 as TNF1 for guanine and TNF2 for adenine. In a multicenter study … (more)
risk factor
(Mar 01, 2006)
no assertion criteria provided
Method: literature only
SEPTIC SHOCK, SUSCEPTIBILITY TO
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000033436.2
First in ClinVar: Apr 04, 2013
Last updated: Sep 09, 2016
Publications:
PubMed (13)
Comment on evidence:
Mira et al. (1999) referred to the TNFA promoter polymorphisms at position -308 as TNF1 for guanine and TNF2 for adenine. In a multicenter study … (more)
risk factor
(Mar 01, 2006)
no assertion criteria provided
Method: literature only
ASTHMA, SUSCEPTIBILITY TO
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000033437.2
First in ClinVar: Apr 04, 2013
Last updated: Sep 09, 2016
Publications:
PubMed (13)
Comment on evidence:
Mira et al. (1999) referred to the TNFA promoter polymorphisms at position -308 as TNF1 for guanine and TNF2 for adenine. In a multicenter study … (more)
risk factor
(Mar 01, 2006)
no assertion criteria provided
Method: literature only
HUMAN IMMUNODEFICIENCY VIRUS DEMENTIA, SUSCEPTIBILITY TO
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000033438.2
First in ClinVar: Apr 04, 2013
Last updated: Sep 09, 2016
Publications:
PubMed (13)
Comment on evidence:
Mira et al. (1999) referred to the TNFA promoter polymorphisms at position -308 as TNF1 for guanine and TNF2 for adenine. In a multicenter study … (more)
risk factor
(Mar 01, 2006)
no assertion criteria provided
Method: literature only
MIGRAINE WITHOUT AURA, SUSCEPTIBILITY TO
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000033439.2
First in ClinVar: Apr 04, 2013
Last updated: Sep 09, 2016
Publications:
PubMed (13)
Comment on evidence:
Mira et al. (1999) referred to the TNFA promoter polymorphisms at position -308 as TNF1 for guanine and TNF2 for adenine. In a multicenter study … (more)
Uncertain significance
(Feb 09, 2021)
no assertion criteria provided
Method: research
Susceptibility to severe coronavirus disease (COVID-19)
Affected status: yes
Allele origin: germline
HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas
Accession: SCV001548220.1
First in ClinVar: Apr 13, 2021
Last updated: Apr 13, 2021
Uncertain significance
(Aug 07, 2021)
no assertion criteria provided
Method: research
Susceptibility to severe coronavirus disease (COVID-19) due to high plasma levels of TNF, TNFR, and/or TNFR4
Affected status: yes
Allele origin: germline
HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas
Accession: SCV001792246.1
First in ClinVar: Jun 18, 2022
Last updated: Jun 18, 2022
Comment:
Differences in plasma levels of TNFR2 according to genotypes
Affects
(Oct 20, 2021)
no assertion criteria provided
Method: case-control
Endometriosis
Affected status: yes
Allele origin: somatic
Laboratorio de Investigación del Departamento de Salud,Universidad Iberoamericana A.C.
Accession: SCV002073726.1
First in ClinVar: Jun 18, 2022
Last updated: Jun 18, 2022
Comment:
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 … (more)
Sex: female
Ethnicity/Population group: Mexican mestizo
Geographic origin: Mexico

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Association between tumor necrosis factor-α (TNF-α) promoter -308 G/A and response to TNF-α blockers in rheumatoid arthritis: a meta-analysis. Zeng Z Modern rheumatology 2013 PMID: 22760475
TNF-alpha-308 G/A polymorphism and responsiveness to TNF-alpha blockade therapy in moderate to severe rheumatoid arthritis: a systematic review and meta-analysis. O'Rielly DD The pharmacogenomics journal 2009 PMID: 19365401
Association of the tumour necrosis factor-308 variant with differential response to anti-TNF agents in the treatment of rheumatoid arthritis. Maxwell JR Human molecular genetics 2008 PMID: 18713756
Influence of -308 A/G polymorphism in the tumor necrosis factor alpha gene on etanercept treatment in rheumatoid arthritis. Guis S Arthritis and rheumatism 2007 PMID: 18050183
The -308 tumour necrosis factor-alpha gene polymorphism predicts therapeutic response to TNFalpha-blockers in rheumatoid arthritis and spondyloarthritis patients. Seitz M Rheumatology (Oxford, England) 2007 PMID: 16720636
Association of TNF-alpha -308 G/A polymorphism with responsiveness to TNF-alpha-blockers in rheumatoid arthritis: a meta-analysis. Lee YH Rheumatology international 2006 PMID: 16909270
An association between asthma and TNF-308G/A polymorphism: meta-analysis. Aoki T Journal of human genetics 2006 PMID: 16865291
Meta-analysis of TNF-alpha promoter -308 A/G polymorphism and SLE susceptibility. Lee YH European journal of human genetics : EJHG 2006 PMID: 16418737
Association between the tumor necrosis factor-alpha -308 G/A gene polymorphism and migraine. Rainero I Neurology 2004 PMID: 14718719
Association of tumor necrosis factor polymorphisms with asthma and serum total IgE. Shin HD Human molecular genetics 2004 PMID: 14681301
Genetic markers for the efficacy of tumour necrosis factor blocking therapy in rheumatoid arthritis. Padyukov L Annals of the rheumatic diseases 2003 PMID: 12759288
Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity. Balding J Arthritis and rheumatism 2003 PMID: 12746914
Association between G-308A polymorphism of the tumor necrosis factor-alpha gene and 24-hour ambulatory blood pressure values in type 1 diabetic adolescents. Krikovszky D Clinical genetics 2002 PMID: 12485196
Relation between tumour necrosis factor polymorphism TNFalpha-308 and risk of asthma. Witte JS European journal of human genetics : EJHG 2002 PMID: 11896460
Association of polymorphisms and allelic combinations in the tumour necrosis factor-alpha-complement MHC region with coronary artery disease. Szalai C Journal of medical genetics 2002 PMID: 11826025
Increased frequency of the tumor necrosis factor-alpha-308 A allele in adults with human immunodeficiency virus dementia. Quasney MW Annals of neurology 2001 PMID: 11506397
Tumor necrosis factor-alpha promoter polymorphism TNF2 is associated with a stronger delayed-type hypersensitivity reaction in the skin of borderline tuberculoid leprosy patients. Moraes MO Immunogenetics 2001 PMID: 11261930
Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study. Mira JP JAMA 1999 PMID: 10450718
Genetic contribution of the tumor necrosis factor region in Guillain-Barré syndrome. Ma JJ Annals of neurology 1998 PMID: 9818939
Comparative analysis of the genetic associations of HLA-DR3 and tumour necrosis factor alpha with human IDDM. Cox A Diabetologia 1994 PMID: 8056188
https://www.pharmgkb.org/clinicalAnnotation/655384799 - - - -
https://www.pharmgkb.org/variant/PA166156997 - - - -

Text-mined citations for rs1800629...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 11, 2022