rs149579135

chr1-2561507-AG-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003820.4(TNFRSF14):c.552-165del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00037 in 1,536,412 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (1 hom.)
• Consequence: TNFRSF14 NM_003820.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.0690

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF14	NM_003820.4	c.552-165del		intron_variant		ENST00000355716.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF14	ENST00000355716.5	c.552-165del		intron_variant		1	NM_003820.4	P1

Frequencies

GnomAD3 genomes AF: 0.00159 AC: 242 AN: 151880 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00518

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.000416 AC: 60 AN: 144336 Hom.: 1 AF XY: 0.000306 AC XY: 24 AN XY: 78434

Gnomad AFR exome AF: 0.00545

Gnomad AMR exome AF: 0.000585

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000440

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000737

Gnomad OTH exome AF: 0.000731

GnomAD4 exome AF: 0.000235 AC: 326 AN: 1384414 Hom.: 1 Cov.: 31 AF XY: 0.000232 AC XY: 158 AN XY: 681604

Gnomad4 AFR exome AF: 0.00560

Gnomad4 AMR exome AF: 0.000699

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000378

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000859

Gnomad4 OTH exome AF: 0.000525

GnomAD4 genome AF: 0.00160 AC: 243 AN: 151998 Hom.: 0 Cov.: 32 AF XY: 0.00159 AC XY: 118 AN XY: 74290

Gnomad4 AFR AF: 0.00519

Gnomad4 AMR AF: 0.000720

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000912 Hom.: 0

Bravo AF: 0.00198

Asia WGS AF: 0.000577 AC: 2 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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs149579135; hg19: chr1-2492946;