rs2234162

Variant names:

• chr1-2559866-C-T
• rs2234162
• NM_003820.4:c.348C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-2559866-C-T
• chr1-2559866-C-A
• chr1-2559866-C-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP7 BS1_Supporting BS2

The NM_003820.4(TNFRSF14):​c.348C>T​(p.Asn116Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,606,804 control chromosomes in the GnomAD database, including 170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.013 (20 hom., cov: 33)
  • Exomes 𝑓: 0.013 (150 hom.)
• Consequence: TNFRSF14 NM_003820.4 synonymous
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.992
• Publications: 9 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-0.992 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0129 (1964/152334) while in subpopulation AMR AF = 0.0246 (376/15304). AF 95% confidence interval is 0.0225. There are 20 homozygotes in GnomAd4. There are 975 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003820.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF14	NM_003820.4	MANE Select	c.348C>T	p.Asn116Asn	synonymous	Exon 4 of 8	NP_003811.2
	TNFRSF14	NM_001297605.2		c.348C>T	p.Asn116Asn	synonymous	Exon 4 of 7	NP_001284534.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF14	ENST00000355716.5	TSL:1 MANE Select	c.348C>T	p.Asn116Asn	synonymous	Exon 4 of 8	ENSP00000347948.4	Q92956-1
	TNFRSF14	ENST00000475523.5	TSL:1	n.585C>T		non_coding_transcript_exon	Exon 2 of 6
	TNFRSF14	ENST00000860787.1		c.612C>T	p.Asn204Asn	synonymous	Exon 4 of 8	ENSP00000530846.1

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1955 AN: 152218 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.00838

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.0118 AC: 2765 AN: 234464 AF XY: 0.0110

Gnomad AFR exome AF: 0.0103

Gnomad AMR exome AF: 0.0234

Gnomad ASJ exome AF: 0.00422

Gnomad EAS exome AF: 0.00487

Gnomad FIN exome AF: 0.00932

Gnomad NFE exome AF: 0.0133

Gnomad OTH exome AF: 0.00904

GnomAD4 exome AF: 0.0125 AC: 18214 AN: 1454470 Hom.: 150 Cov.: 34 AF XY: 0.0122 AC XY: 8787 AN XY: 722826

African (AFR) AF: 0.0105 AC: 349 AN: 33388

American (AMR) AF: 0.0228 AC: 1004 AN: 43946

Ashkenazi Jewish (ASJ) AF: 0.00377 AC: 98 AN: 25964

East Asian (EAS) AF: 0.00360 AC: 142 AN: 39432

South Asian (SAS) AF: 0.00286 AC: 243 AN: 84914

European-Finnish (FIN) AF: 0.00932 AC: 482 AN: 51698

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5762

European-Non Finnish (NFE) AF: 0.0137 AC: 15216 AN: 1109286

Other (OTH) AF: 0.0112 AC: 671 AN: 60080

GnomAD4 genome AF: 0.0129 AC: 1964 AN: 152334 Hom.: 20 Cov.: 33 AF XY: 0.0131 AC XY: 975 AN XY: 74476

African (AFR) AF: 0.0108 AC: 447 AN: 41578

American (AMR) AF: 0.0246 AC: 376 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3472

East Asian (EAS) AF: 0.00463 AC: 24 AN: 5182

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4832

European-Finnish (FIN) AF: 0.00838 AC: 89 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0142 AC: 968 AN: 68024

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.0117 Hom.: 5

Bravo AF: 0.0128

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.68
PhyloP100		-0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2234162; hg19: chr1-2491305; COSMIC: COSV100859072; COSMIC: COSV100859072;