chr6-31575254-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

drug response reviewed by expert panel U:2O:9

Conservation

PhyloP100: 0.0180
Variant links:

Genome browser will be placed here

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 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
show subpopulations
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
show subpopulations
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
show subpopulations
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
show subpopulations
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:2Other:9
Revision: reviewed by expert panel
LINK: link

Submissions by phenotype

Susceptibility to severe coronavirus disease (COVID-19) Uncertain:1
Uncertain significance, no assertion criteria providedresearchHLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio VillegasFeb 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 providedresearchHLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio VillegasAug 07, 2021Differences in plasma levels of TNFR2 according to genotypes -
Malaria, cerebral, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMMar 01, 2006- -
Systemic lupus erythematosus, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMMar 01, 2006- -
Inherited susceptibility to asthma Other:1
risk factor, no assertion criteria providedliterature onlyOMIMMar 01, 2006- -
etanercept response - Efficacy Other:1
drug response, reviewed by expert panelcurationPharmGKBMar 24, 2021PharmGKB 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 providedliterature onlyOMIMMar 01, 2006- -
MIGRAINE WITHOUT AURA, SUSCEPTIBILITY TO Other:1
risk factor, no assertion criteria providedliterature onlyOMIMMar 01, 2006- -
SEPTIC SHOCK, SUSCEPTIBILITY TO Other:1
risk factor, no assertion criteria providedliterature onlyOMIMMar 01, 2006- -
HUMAN IMMUNODEFICIENCY VIRUS DEMENTIA, SUSCEPTIBILITY TO Other:1
risk factor, no assertion criteria providedliterature onlyOMIMMar 01, 2006- -
Endometriosis Other:1
Affects, no assertion criteria providedcase-controlLaboratorio de Investigación del Departamento de Salud, Universidad Iberoamericana A.C.Oct 20, 2021Mexican 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1800629; hg19: chr6-31543031; API