Variant rs2234167 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003820.4(TNFRSF14):c.721G>A(p.Val241Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,613,286 control chromosomes in the GnomAD database, including 14,956 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1178 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13778 hom. )

Consequence

TNFRSF14
NM_003820.4 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -2.03

Variant links:

Genes affected

TNFRSF14 (HGNC:11912): (TNF receptor superfamily member 14) This gene encodes a member of the TNF (tumor necrosis factor) receptor superfamily. The encoded protein functions in signal transduction pathways that activate inflammatory and inhibitory T-cell immune response. It binds herpes simplex virus (HSV) viral envelope glycoprotein D (gD), mediating its entry into cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

TNFRSF14 links:

TNFRSF14 (HGNC:):

TNFRSF14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014363527).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF14	NM_003820.4 linkuse as main transcript	c.721G>A	p.Val241Ile	missense_variant	7/8	ENST00000355716.5	NP_003811.2	Q92956-1A0A024R052

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF14	ENST00000355716.5 linkuse as main transcript	c.721G>A	p.Val241Ile	missense_variant	7/8	1	NM_003820.4	ENSP00000347948.4		Q92956-1

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18340

AN:

151958

Hom.:

1176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0915

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.0984

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.0519

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.149

GnomAD3 exomes

AF:

0.127

AC:

31923

AN:

250422

Hom.:

2290

AF XY:

0.133

AC XY:

18096

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.0908

Gnomad AMR exome

AF:

0.0855

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.0548

Gnomad SAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.133

GnomAD4 exome

AF:

0.134

AC:

195098

AN:

1461210

Hom.:

13778

Cov.:

AF XY:

0.136

AC XY:

99088

AN XY:

726906

show subpopulations

Gnomad4 AFR exome

AF:

0.0960

Gnomad4 AMR exome

AF:

0.0874

Gnomad4 ASJ exome

AF:

0.147

Gnomad4 EAS exome

AF:

0.0441

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.124

Gnomad4 NFE exome

AF:

0.136

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

AF:

0.121

AC:

18350

AN:

152076

Hom.:

1178

Cov.:

AF XY:

0.120

AC XY:

8952

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0916

Gnomad4 AMR

AF:

0.0982

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.0520

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.140

Gnomad4 OTH

AF:

0.149

Alfa

AF:

0.137

Hom.:

3042

Bravo

AF:

0.115

TwinsUK

AF:

0.142

AC:

525

ALSPAC

AF:

0.133

AC:

512

ESP6500AA

AF:

0.0887

AC:

391

ESP6500EA

AF:

0.141

AC:

1213

ExAC

AF:

0.129

AC:

15651

Asia WGS

AF:

0.112

AC:

388

AN:

3478

EpiCase

AF:

0.148

EpiControl

AF:

0.151

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.055

DANN

Benign

0.56

DEOGEN2

Benign

0.10

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.016

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.15

REVEL

Benign

0.14

Sift

Benign

0.51

Sift4G

Benign

0.68

Polyphen

0.085

Vest4

0.035

MPC

0.13

ClinPred

0.00048

GERP RS

-4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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