1-2559170-T-C

Position:

• chr1-2559170-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003820.4(TNFRSF14):​c.305-653T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,366,842 control chromosomes in the GnomAD database, including 23 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 0.0026 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0036 (19 hom.)
• Consequence: TNFRSF14 NM_003820.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -2.83

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF14	NM_003820.4	c.305-653T>C		intron_variant		ENST00000355716.5	NP_003811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF14	ENST00000355716.5	c.305-653T>C		intron_variant		1	NM_003820.4	ENSP00000347948	P1

Frequencies

GnomAD3 genomes AF: 0.00264 AC: 401 AN: 152166 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.00584

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00400

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00321 AC: 425 AN: 132204 Hom.: 2 AF XY: 0.00388 AC XY: 279 AN XY: 71966

Gnomad AFR exome AF: 0.000313

Gnomad AMR exome AF: 0.000618

Gnomad ASJ exome AF: 0.00443

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00671

Gnomad FIN exome AF: 0.00378

Gnomad NFE exome AF: 0.00374

Gnomad OTH exome AF: 0.00270

GnomAD4 exome AF: 0.00362 AC: 4397 AN: 1214558 Hom.: 19 Cov.: 30 AF XY: 0.00376 AC XY: 2231 AN XY: 592664

Gnomad4 AFR exome AF: 0.000354

Gnomad4 AMR exome AF: 0.000589

Gnomad4 ASJ exome AF: 0.00426

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00669

Gnomad4 FIN exome AF: 0.00288

Gnomad4 NFE exome AF: 0.00368

Gnomad4 OTH exome AF: 0.00341

GnomAD4 genome AF: 0.00263 AC: 401 AN: 152284 Hom.: 4 Cov.: 33 AF XY: 0.00277 AC XY: 206 AN XY: 74458

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.00584

Gnomad4 NFE AF: 0.00400

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00470 Hom.: 1

Bravo AF: 0.00192

Asia WGS AF: 0.00115 AC: 4 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.29
DANN	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs148507536; hg19: chr1-2490609;