rs2281852

chr1-2559503-C-Achr1-2559503-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003820.4(TNFRSF14):c.305-320C>A variant causes a intron 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 NM_003820.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.90

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TNFRSF14	NM_003820.4	c.305-320C>A		intron_variant		ENST00000355716.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF14	ENST00000355716.5	c.305-320C>A		intron_variant		1	NM_003820.4	P1

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

GnomAD3 exomes AF: 0.525 AC: 70597 AN: 134594 Hom.: 18852 AF XY: 0.528 AC XY: 38669 AN XY: 73300

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 SAS exome AF: 0.636

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

Gnomad4 AFR exome AF: 0.661

Gnomad4 AMR exome AF: 0.531

Gnomad4 ASJ exome AF: 0.462

Gnomad4 EAS exome AF: 0.493

Gnomad4 SAS exome AF: 0.626

Gnomad4 FIN exome AF: 0.481

Gnomad4 NFE exome AF: 0.489

Gnomad4 OTH exome AF: 0.516

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

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.525

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

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2281852; hg19: chr1-2490942; COSMIC: COSV63185770; COSMIC: COSV63185770;