rs2234167

Variant names:

• chr1-2562891-G-A
• rs2234167
• NM_003820.4:c.721G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-2562891-G-A
• chr1-2562891-G-C
• chr1-2562891-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.12 (1178 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13778 hom.)
• Consequence: TNFRSF14 NM_003820.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -2.03
• Publications: 65 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TNFRSF14	NM_003820.4	c.721G>A	p.Val241Ile	missense_variant	Exon 7 of 8	ENST00000355716.5	NP_003811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF14	ENST00000355716.5	c.721G>A	p.Val241Ile	missense_variant	Exon 7 of 8	1	NM_003820.4	ENSP00000347948.4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18340 AN: 151958 Hom.: 1176 Cov.: 32

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

GnomAD2 exomes AF: 0.127 AC: 31923 AN: 250422 AF XY: 0.133

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 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.: 32 AF XY: 0.136 AC XY: 99088 AN XY: 726906

African (AFR) AF: 0.0960 AC: 3215 AN: 33476

American (AMR) AF: 0.0874 AC: 3909 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 3847 AN: 26130

East Asian (EAS) AF: 0.0441 AC: 1751 AN: 39692

South Asian (SAS) AF: 0.179 AC: 15452 AN: 86242

European-Finnish (FIN) AF: 0.124 AC: 6595 AN: 53242

Middle Eastern (MID) AF: 0.235 AC: 1352 AN: 5764

European-Non Finnish (NFE) AF: 0.136 AC: 150745 AN: 1111586

Other (OTH) AF: 0.136 AC: 8232 AN: 60370

GnomAD4 genome AF: 0.121 AC: 18350 AN: 152076 Hom.: 1178 Cov.: 32 AF XY: 0.120 AC XY: 8952 AN XY: 74342

African (AFR) AF: 0.0916 AC: 3798 AN: 41460

American (AMR) AF: 0.0982 AC: 1502 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3470

East Asian (EAS) AF: 0.0520 AC: 270 AN: 5188

South Asian (SAS) AF: 0.174 AC: 837 AN: 4812

European-Finnish (FIN) AF: 0.136 AC: 1438 AN: 10578

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9522 AN: 67956

Other (OTH) AF: 0.149 AC: 314 AN: 2110

Alfa AF: 0.133 Hom.: 5940

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

Submissions by phenotype

not specified Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.055
DANN	Benign	0.56
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.016	N
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.0
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.14
Sift	Benign	0.51	T
Sift4G	Benign	0.68	T
Polyphen		0.085	B
Vest4		0.035
MPC		0.13
ClinPred		0.00048	T
GERP RS		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.020
gMVP		0.14
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2234167; hg19: chr1-2494330; COSMIC: COSV63187683; COSMIC: COSV63187683;