Variant 1-2556714-A-G 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.50A>G(p.Lys17Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 1,602,598 control chromosomes in the GnomAD database, including 204,775 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 0.55 ( 24325 hom., cov: 33)

Exomes 𝑓: 0.49 ( 180450 hom. )

Consequence

TNFRSF14
NM_003820.4 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -1.27

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-AS1 (HGNC:26966): (TNFRSF14 antisense RNA 1)

TNFRSF14-AS1 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=2.6974876E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 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.50A>G	p.Lys17Arg	missense_variant	1/8	ENST00000355716.5	NP_003811.2
TNFRSF14-AS1	NR_037844.2 linkuse as main transcript	n.36-18T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF14	ENST00000355716.5 linkuse as main transcript	c.50A>G	p.Lys17Arg	missense_variant	1/8	1	NM_003820.4	ENSP00000347948	P1	Q92956-1
TNFRSF14-AS1	ENST00000416860.3 linkuse as main transcript	n.56-18T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.554

AC:

84223

AN:

151926

Hom.:

24294

Cov.:

show subpopulations

Gnomad AFR

AF:

0.719

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.538

Gnomad ASJ

AF:

0.452

Gnomad EAS

AF:

0.502

Gnomad SAS

AF:

0.639

Gnomad FIN

AF:

0.497

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.474

Gnomad OTH

AF:

0.524

GnomAD3 exomes

AF:

0.514

AC:

121076

AN:

235732

Hom.:

31748

AF XY:

0.514

AC XY:

65717

AN XY:

127924

show subpopulations

Gnomad AFR exome

AF:

0.727

Gnomad AMR exome

AF:

0.511

Gnomad ASJ exome

AF:

0.442

Gnomad EAS exome

AF:

0.491

Gnomad SAS exome

AF:

0.633

Gnomad FIN exome

AF:

0.489

Gnomad NFE exome

AF:

0.467

Gnomad OTH exome

AF:

0.495

GnomAD4 exome

AF:

0.495

AC:

717835

AN:

1450556

Hom.:

180450

Cov.:

AF XY:

0.498

AC XY:

359180

AN XY:

720804

show subpopulations

Gnomad4 AFR exome

AF:

0.731

Gnomad4 AMR exome

AF:

0.511

Gnomad4 ASJ exome

AF:

0.454

Gnomad4 EAS exome

AF:

0.489

Gnomad4 SAS exome

AF:

0.624

Gnomad4 FIN exome

AF:

0.479

Gnomad4 NFE exome

AF:

0.478

Gnomad4 OTH exome

AF:

0.513

GnomAD4 genome

AF:

0.554

AC:

84301

AN:

152042

Hom.:

24325

Cov.:

AF XY:

0.556

AC XY:

41315

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.719

Gnomad4 AMR

AF:

0.538

Gnomad4 ASJ

AF:

0.452

Gnomad4 EAS

AF:

0.501

Gnomad4 SAS

AF:

0.640

Gnomad4 FIN

AF:

0.497

Gnomad4 NFE

AF:

0.474

Gnomad4 OTH

AF:

0.529

Alfa

AF:

0.497

Hom.:

12431

Bravo

AF:

0.557

TwinsUK

AF:

0.492

AC:

1826

ALSPAC

AF:

0.479

AC:

1847

ESP6500AA

AF:

0.726

AC:

3193

ESP6500EA

AF:

0.472

AC:

4058

ExAC

AF:

0.510

AC:

61543

Asia WGS

AF:

0.637

AC:

2216

AN:

3478

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

0.069

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Benign

7.6

DANN

Benign

0.93

DEOGEN2

Benign

0.0079

T;T;T;T;.;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.014

MetaRNN

Benign

0.0000027

T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.2

.;.;.;.;.;L

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.59

N;N;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.47

T;T;T;T;T;T

Sift4G

Benign

0.18

T;T;T;T;T;T

Polyphen

0.39

.;.;.;.;.;B

Vest4

0.030, 0.031

MPC

0.14

ClinPred

0.0080

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.033

gMVP

0.42

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