Variant chr19-6665009-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001376887.1(TNFSF14):c.640A>G(p.Lys214Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 1,613,832 control chromosomes in the GnomAD database, including 722,436 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.95 ( 69180 hom., cov: 32)

Exomes 𝑓: 0.95 ( 653256 hom. )

Consequence

TNFSF14
NM_001376887.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0570

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.5369017E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF14	NM_001376887.1 linkuse as main transcript	c.640A>G	p.Lys214Glu	missense_variant	4/4	ENST00000675206.1	NP_001363816.1
TNFSF14	NM_003807.5 linkuse as main transcript	c.640A>G	p.Lys214Glu	missense_variant	5/5		NP_003798.2	O43557-1
TNFSF14	NM_172014.3 linkuse as main transcript	c.532A>G	p.Lys178Glu	missense_variant	4/4		NP_742011.2	O43557-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TNFSF14	ENST00000675206.1 linkuse as main transcript	c.640A>G	p.Lys214Glu	missense_variant	4/4		NM_001376887.1	ENSP00000502837.1	O43557-1
TNFSF14	ENST00000599359.1 linkuse as main transcript	c.640A>G	p.Lys214Glu	missense_variant	5/5	1		ENSP00000469049.1	O43557-1
TNFSF14	ENST00000245912.7 linkuse as main transcript	c.532A>G	p.Lys178Glu	missense_variant	4/4	1		ENSP00000245912.3	O43557-2

Frequencies

GnomAD3 genomes

AF:

0.953

AC:

145000

AN:

152194

Hom.:

69124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.986

Gnomad AMI

AF:

0.779

Gnomad AMR

AF:

0.933

Gnomad ASJ

AF:

0.907

Gnomad EAS

AF:

0.928

Gnomad SAS

AF:

0.965

Gnomad FIN

AF:

0.946

Gnomad MID

AF:

0.972

Gnomad NFE

AF:

0.944

Gnomad OTH

AF:

0.947

GnomAD3 exomes

AF:

0.947

AC:

237897

AN:

251330

Hom.:

112629

AF XY:

0.947

AC XY:

128635

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.985

Gnomad AMR exome

AF:

0.946

Gnomad ASJ exome

AF:

0.910

Gnomad EAS exome

AF:

0.922

Gnomad SAS exome

AF:

0.962

Gnomad FIN exome

AF:

0.942

Gnomad NFE exome

AF:

0.945

Gnomad OTH exome

AF:

0.941

GnomAD4 exome

AF:

0.945

AC:

1381778

AN:

1461520

Hom.:

653256

Cov.:

AF XY:

0.946

AC XY:

687629

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.988

Gnomad4 AMR exome

AF:

0.946

Gnomad4 ASJ exome

AF:

0.907

Gnomad4 EAS exome

AF:

0.934

Gnomad4 SAS exome

AF:

0.963

Gnomad4 FIN exome

AF:

0.942

Gnomad4 NFE exome

AF:

0.944

Gnomad4 OTH exome

AF:

0.944

GnomAD4 genome

AF:

0.953

AC:

145115

AN:

152312

Hom.:

69180

Cov.:

AF XY:

0.953

AC XY:

70986

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.986

Gnomad4 AMR

AF:

0.933

Gnomad4 ASJ

AF:

0.907

Gnomad4 EAS

AF:

0.928

Gnomad4 SAS

AF:

0.965

Gnomad4 FIN

AF:

0.946

Gnomad4 NFE

AF:

0.944

Gnomad4 OTH

AF:

0.947

Alfa

AF:

0.943

Hom.:

171164

Bravo

AF:

0.952

TwinsUK

AF:

0.943

AC:

3498

ALSPAC

AF:

0.944

AC:

3640

ESP6500AA

AF:

0.984

AC:

4336

ESP6500EA

AF:

0.945

AC:

8126

ExAC

AF:

0.948

AC:

115148

Asia WGS

AF:

0.958

AC:

3332

AN:

3478

EpiCase

AF:

0.943

EpiControl

AF:

0.944

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.042

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.30

DEOGEN2

Uncertain

0.57

.;D

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.0099

LIST_S2

Benign

0.19

T;T

MetaRNN

Benign

0.0000035

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.88

.;N

PrimateAI

Uncertain

0.56

REVEL

Benign

0.28

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.082

MPC

0.46

ClinPred

0.0022

GERP RS

2.3

Varity_R

0.14

gMVP

0.62

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over