1-2559459-C-A

Position:

• chr1-2559459-C-A

Variant summary

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

The NM_003820.4(TNFRSF14):​c.305-364C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 1,414,678 control chromosomes in the GnomAD database, including 189,792 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 (26210 hom., cov: 32)
  • Exomes 𝑓: 0.51 (163582 hom.)
• Consequence: TNFRSF14 NM_003820.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.0550

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF14	NM_003820.4	c.305-364C>A		intron_variant		ENST00000355716.5	NP_003811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF14	ENST00000355716.5	c.305-364C>A		intron_variant		1	NM_003820.4	ENSP00000347948	P1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87219 AN: 151398 Hom.: 26162 Cov.: 32

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.550

GnomAD3 exomes AF: 0.541 AC: 72790 AN: 134530 Hom.: 20180 AF XY: 0.544 AC XY: 39825 AN XY: 73252

Gnomad AFR exome AF: 0.771

Gnomad AMR exome AF: 0.540

Gnomad ASJ exome AF: 0.456

Gnomad EAS exome AF: 0.539

Gnomad SAS exome AF: 0.654

Gnomad FIN exome AF: 0.486

Gnomad NFE exome AF: 0.487

Gnomad OTH exome AF: 0.518

GnomAD4 exome AF: 0.509 AC: 642565 AN: 1263168 Hom.: 163582 Cov.: 62 AF XY: 0.512 AC XY: 317071 AN XY: 618694

Gnomad4 AFR exome AF: 0.764

Gnomad4 AMR exome AF: 0.538

Gnomad4 ASJ exome AF: 0.463

Gnomad4 EAS exome AF: 0.521

Gnomad4 SAS exome AF: 0.642

Gnomad4 FIN exome AF: 0.484

Gnomad4 NFE exome AF: 0.490

Gnomad4 OTH exome AF: 0.526

GnomAD4 genome AF: 0.576 AC: 87317 AN: 151510 Hom.: 26210 Cov.: 32 AF XY: 0.578 AC XY: 42775 AN XY: 74054

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.554

Alfa AF: 0.491 Hom.: 5098

Bravo AF: 0.580

Asia WGS AF: 0.678 AC: 2361 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	-0.91
CADD	Benign	0.88
DANN	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2257763; hg19: chr1-2490898; COSMIC: COSV63187619; COSMIC: COSV63187619;