Variant chr6-31575254-G-A details in Genebe, Genetics Data Aggregator

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

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/exons	MANE	Protein	UniProt

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20989

AN:

152008

Hom.:

1578

Cov.:

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.:

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.:

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 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

- -

Systemic lupus erythematosus, 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

- -

MIGRAINE WITHOUT AURA, 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

- -

HUMAN IMMUNODEFICIENCY VIRUS DEMENTIA, 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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over