Variant rs2291668 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001376887.1(TNFSF14):c.147C>T(p.Ala49=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,613,624 control chromosomes in the GnomAD database, including 26,132 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2439 hom., cov: 31)

Exomes 𝑓: 0.17 ( 23693 hom. )

Consequence

TNFSF14
NM_001376887.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.93

Variant links:

Genes affected

TNFSF14 (HGNC:11930): (TNF superfamily member 14) The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF14, which is a member of the tumor necrosis factor receptor superfamily, and which is also known as a herpesvirus entry mediator (HVEM). This protein may function as a costimulatory factor for the activation of lymphoid cells and as a deterrent to infection by herpesvirus. This protein has been shown to stimulate the proliferation of T cells, and trigger apoptosis of various tumor cells. This protein is also reported to prevent tumor necrosis factor alpha mediated apoptosis in primary hepatocyte. Two alternatively spliced transcript variant encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

TNFSF14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP7

Synonymous conserved (PhyloP=-4.93 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TNFSF14	NM_001376887.1 linkuse as main transcript	c.147C>T	p.Ala49=	synonymous_variant	1/4	ENST00000675206.1	NP_001363816.1
TNFSF14	NM_003807.5 linkuse as main transcript	c.147C>T	p.Ala49=	synonymous_variant	2/5		NP_003798.2
TNFSF14	NM_172014.3 linkuse as main transcript	c.111+36C>T		intron_variant			NP_742011.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF14	ENST00000675206.1 linkuse as main transcript	c.147C>T	p.Ala49=	synonymous_variant	1/4		NM_001376887.1	ENSP00000502837	P1	O43557-1
TNFSF14	ENST00000599359.1 linkuse as main transcript	c.147C>T	p.Ala49=	synonymous_variant	2/5	1		ENSP00000469049	P1	O43557-1
TNFSF14	ENST00000245912.7 linkuse as main transcript	c.111+36C>T		intron_variant		1		ENSP00000245912		O43557-2

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25365

AN:

151700

Hom.:

2438

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.313

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.159

GnomAD3 exomes

AF:

0.188

AC:

47194

AN:

250688

Hom.:

5085

AF XY:

0.183

AC XY:

24833

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.264

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.274

Gnomad SAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.296

Gnomad NFE exome

AF:

0.161

Gnomad OTH exome

AF:

0.179

GnomAD4 exome

AF:

0.173

AC:

253049

AN:

1461806

Hom.:

23693

Cov.:

AF XY:

0.171

AC XY:

124615

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.0964

Gnomad4 AMR exome

AF:

0.256

Gnomad4 ASJ exome

AF:

0.138

Gnomad4 EAS exome

AF:

0.335

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.283

Gnomad4 NFE exome

AF:

0.165

Gnomad4 OTH exome

AF:

0.171

GnomAD4 genome

AF:

0.167

AC:

25391

AN:

151818

Hom.:

2439

Cov.:

AF XY:

0.175

AC XY:

12960

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.108

Gnomad4 AMR

AF:

0.218

Gnomad4 ASJ

AF:

0.135

Gnomad4 EAS

AF:

0.278

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.313

Gnomad4 NFE

AF:

0.164

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.157

Hom.:

932

Bravo

AF:

0.160

Asia WGS

AF:

0.207

AC:

720

AN:

3478

EpiCase

AF:

0.161

EpiControl

AF:

0.154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.69

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over