Variant 1-2559867-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_003820.4(TNFRSF14):c.349G>A(p.Ala117Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00885 in 1,606,292 control chromosomes in the GnomAD database, including 142 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 0.015 ( 36 hom., cov: 33)

Exomes 𝑓: 0.0082 ( 106 hom. )

Consequence

TNFRSF14
NM_003820.4 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -1.25

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023900867).

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0153 (2332/152350) while in subpopulation EAS AF= 0.0399 (207/5188). AF 95% confidence interval is 0.0355. There are 36 homozygotes in gnomad4. There are 1091 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF14	NM_003820.4 linkuse as main transcript	c.349G>A	p.Ala117Thr	missense_variant	4/8	ENST00000355716.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF14	ENST00000355716.5 linkuse as main transcript	c.349G>A	p.Ala117Thr	missense_variant	4/8	1	NM_003820.4	P1	Q92956-1

Frequencies

GnomAD3 genomes

AF:

0.0152

AC:

2321

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0350

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00621

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0402

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00629

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.0107

AC:

2503

AN:

233130

Hom.:

AF XY:

0.0102

AC XY:

1288

AN XY:

126526

show subpopulations

Gnomad AFR exome

AF:

0.0368

Gnomad AMR exome

AF:

0.00355

Gnomad ASJ exome

AF:

0.00175

Gnomad EAS exome

AF:

0.0383

Gnomad SAS exome

AF:

0.0141

Gnomad FIN exome

AF:

0.00232

Gnomad NFE exome

AF:

0.00632

Gnomad OTH exome

AF:

0.00890

GnomAD4 exome

AF:

0.00817

AC:

11881

AN:

1453942

Hom.:

106

Cov.:

AF XY:

0.00819

AC XY:

5918

AN XY:

722526

show subpopulations

Gnomad4 AFR exome

AF:

0.0366

Gnomad4 AMR exome

AF:

0.00408

Gnomad4 ASJ exome

AF:

0.00185

Gnomad4 EAS exome

AF:

0.0275

Gnomad4 SAS exome

AF:

0.0150

Gnomad4 FIN exome

AF:

0.00254

Gnomad4 NFE exome

AF:

0.00659

Gnomad4 OTH exome

AF:

0.00987

GnomAD4 genome

AF:

0.0153

AC:

2332

AN:

152350

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

1091

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0352

Gnomad4 AMR

AF:

0.00621

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.0399

Gnomad4 SAS

AF:

0.0153

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00629

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00874

Hom.:

Bravo

AF:

0.0165

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.0339

AC:

149

ESP6500EA

AF:

0.00641

AC:

ExAC

AF:

0.0105

AC:

1266

Asia WGS

AF:

0.0310

AC:

108

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

0.071

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.063

DANN

Benign

0.68

DEOGEN2

Benign

0.17

T;T;T;T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0028

MetaRNN

Benign

0.0024

T;T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-2.0

.;.;.;.;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

3.5

N;N;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.80

.;.;.;.;.;P

Vest4

0.016, 0.042

MPC

0.15

ClinPred

0.0090

GERP RS

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.058

gMVP

0.61

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