chr1-2559766-C-T

Position:

• chr1-2559766-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.305-57C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,558,776 control chromosomes in the GnomAD database, including 214,939 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 0.58 (26835 hom., cov: 33)
  • Exomes 𝑓: 0.51 (188104 hom.)
• Consequence: TNFRSF14 NM_003820.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.93

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF14	NM_003820.4	c.305-57C>T		intron_variant		ENST00000355716.5	NP_003811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF14	ENST00000355716.5	c.305-57C>T		intron_variant		1	NM_003820.4	ENSP00000347948	P1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88150 AN: 151980 Hom.: 26787 Cov.: 33

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.548

GnomAD3 exomes AF: 0.553 AC: 93669 AN: 169440 Hom.: 26473 AF XY: 0.553 AC XY: 50934 AN XY: 92036

Gnomad AFR exome AF: 0.797

Gnomad AMR exome AF: 0.548

Gnomad ASJ exome AF: 0.460

Gnomad EAS exome AF: 0.554

Gnomad SAS exome AF: 0.656

Gnomad FIN exome AF: 0.509

Gnomad NFE exome AF: 0.503

Gnomad OTH exome AF: 0.524

GnomAD4 exome AF: 0.513 AC: 721736 AN: 1406678 Hom.: 188104 Cov.: 95 AF XY: 0.516 AC XY: 359477 AN XY: 696134

Gnomad4 AFR exome AF: 0.785

Gnomad4 AMR exome AF: 0.544

Gnomad4 ASJ exome AF: 0.464

Gnomad4 EAS exome AF: 0.524

Gnomad4 SAS exome AF: 0.640

Gnomad4 FIN exome AF: 0.492

Gnomad4 NFE exome AF: 0.495

Gnomad4 OTH exome AF: 0.532

GnomAD4 genome AF: 0.580 AC: 88252 AN: 152098 Hom.: 26835 Cov.: 33 AF XY: 0.581 AC XY: 43204 AN XY: 74354

Gnomad4 AFR AF: 0.768

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.553

Alfa AF: 0.445 Hom.: 2878

Bravo AF: 0.584

Asia WGS AF: 0.673 AC: 2343 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	-0.90
CADD	Benign	0.97
DANN	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2234161; hg19: chr1-2491205; COSMIC: COSV63185654; COSMIC: COSV63185654;