rs587777990

Variant names:

• chr1-2559503-C-A
• rs2281852
• ENST00000475523.5:n.222C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-2559503-C-A
• chrNT_187515.1-110693-C-A
• chr1-2559503-C-T
• chrNT_187515.1-110693-C-T

Variant summary

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

The ENST00000475523.5(TNFRSF14):​n.222C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 1,472,328 control chromosomes in the GnomAD database, including 191,666 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 0.54 (22913 hom., cov: 34)
  • Exomes 𝑓: 0.50 (168753 hom.)
• Consequence: TNFRSF14 ENST00000475523.5 non_coding_transcript_exon
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.90
• Publications: 24 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 (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF14	NM_003820.4	c.305-320C>A		intron_variant	Intron 3 of 7	ENST00000355716.5	NP_003811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF14	ENST00000355716.5	c.305-320C>A		intron_variant	Intron 3 of 7	1	NM_003820.4	ENSP00000347948.4

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82469 AN: 151920 Hom.: 22890 Cov.: 34

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.521

GnomAD2 exomes AF: 0.525 AC: 70597 AN: 134594 AF XY: 0.528

Gnomad AFR exome AF: 0.659

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.454

Gnomad EAS exome AF: 0.498

Gnomad FIN exome AF: 0.484

Gnomad NFE exome AF: 0.479

Gnomad OTH exome AF: 0.505

GnomAD4 exome AF: 0.503 AC: 663495 AN: 1320290 Hom.: 168753 Cov.: 81 AF XY: 0.506 AC XY: 328096 AN XY: 648554

African (AFR) AF: 0.661 AC: 20283 AN: 30680

American (AMR) AF: 0.531 AC: 17795 AN: 33536

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 11002 AN: 23790

East Asian (EAS) AF: 0.493 AC: 15109 AN: 30642

South Asian (SAS) AF: 0.626 AC: 48670 AN: 77808

European-Finnish (FIN) AF: 0.481 AC: 12426 AN: 25820

Middle Eastern (MID) AF: 0.536 AC: 2901 AN: 5412

European-Non Finnish (NFE) AF: 0.489 AC: 507161 AN: 1038102

Other (OTH) AF: 0.516 AC: 28148 AN: 54500

GnomAD4 genome AF: 0.543 AC: 82536 AN: 152038 Hom.: 22913 Cov.: 34 AF XY: 0.545 AC XY: 40536 AN XY: 74332

African (AFR) AF: 0.655 AC: 27156 AN: 41468

American (AMR) AF: 0.550 AC: 8406 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1583 AN: 3472

East Asian (EAS) AF: 0.503 AC: 2599 AN: 5172

South Asian (SAS) AF: 0.642 AC: 3096 AN: 4824

European-Finnish (FIN) AF: 0.508 AC: 5373 AN: 10572

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32807 AN: 67920

Other (OTH) AF: 0.525 AC: 1107 AN: 2108

Alfa AF: 0.438 Hom.: 3679

Bravo AF: 0.542

Asia WGS AF: 0.637 AC: 2216 AN: 3478

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.62
DANN	Benign	0.26
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2281852; hg19: chr1-2490942; COSMIC: COSV63185770; COSMIC: COSV63185770;