rs2291668

Variant names:

• chr19-6669923-G-A
• rs2291668
• NM_001376887.1:c.147C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-6669923-G-A
• chr19-6669923-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001376887.1(TNFSF14):​c.147C>T​(p.Ala49Ala) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.93
• Publications: 22 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TNFSF14	NM_001376887.1	c.147C>T	p.Ala49Ala	synonymous_variant	Exon 1 of 4	ENST00000675206.1	NP_001363816.1
TNFSF14	NM_003807.5	c.147C>T	p.Ala49Ala	synonymous_variant	Exon 2 of 5		NP_003798.2
TNFSF14	NM_172014.3	c.111+36C>T		intron_variant	Intron 1 of 3		NP_742011.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF14	ENST00000675206.1	c.147C>T	p.Ala49Ala	synonymous_variant	Exon 1 of 4		NM_001376887.1	ENSP00000502837.1
TNFSF14	ENST00000599359.1	c.147C>T	p.Ala49Ala	synonymous_variant	Exon 2 of 5	1		ENSP00000469049.1
TNFSF14	ENST00000245912.7	c.111+36C>T		intron_variant	Intron 1 of 3	1		ENSP00000245912.3
TNFSF14	ENST00000850589.1	n.147C>T		non_coding_transcript_exon_variant	Exon 1 of 5			ENSP00000520876.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25365 AN: 151700 Hom.: 2438 Cov.: 31

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

GnomAD2 exomes AF: 0.188 AC: 47194 AN: 250688 AF XY: 0.183

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 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.: 35 AF XY: 0.171 AC XY: 124615 AN XY: 727208

African (AFR) AF: 0.0964 AC: 3227 AN: 33480

American (AMR) AF: 0.256 AC: 11428 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 3599 AN: 26136

East Asian (EAS) AF: 0.335 AC: 13293 AN: 39698

South Asian (SAS) AF: 0.133 AC: 11499 AN: 86256

European-Finnish (FIN) AF: 0.283 AC: 15104 AN: 53348

Middle Eastern (MID) AF: 0.0947 AC: 546 AN: 5766

European-Non Finnish (NFE) AF: 0.165 AC: 184020 AN: 1112006

Other (OTH) AF: 0.171 AC: 10333 AN: 60392

GnomAD4 genome AF: 0.167 AC: 25391 AN: 151818 Hom.: 2439 Cov.: 31 AF XY: 0.175 AC XY: 12960 AN XY: 74180

African (AFR) AF: 0.108 AC: 4464 AN: 41412

American (AMR) AF: 0.218 AC: 3328 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 469 AN: 3466

East Asian (EAS) AF: 0.278 AC: 1430 AN: 5138

South Asian (SAS) AF: 0.133 AC: 640 AN: 4798

European-Finnish (FIN) AF: 0.313 AC: 3288 AN: 10518

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11161 AN: 67936

Other (OTH) AF: 0.160 AC: 335 AN: 2096

Alfa AF: 0.162 Hom.: 1593

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
PhyloP100		-4.9
PromoterAI		0.021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2291668; hg19: chr19-6669934; COSMIC: COSV55590735;