Variant rs587777996 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_003820.4(TNFRSF14):c.305-98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 1,538,132 control chromosomes in the GnomAD database, including 909 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 0.027 ( 74 hom., cov: 34)

Exomes 𝑓: 0.033 ( 835 hom. )

Consequence

TNFRSF14
NM_003820.4 intron

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -1.66

Variant links:

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]

TNFRSF14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0265 (4042/152294) while in subpopulation NFE AF= 0.0385 (2620/68014). AF 95% confidence interval is 0.0373. There are 74 homozygotes in gnomad4. There are 1968 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 74 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF14	NM_003820.4 linkuse as main transcript	c.305-98G>A		intron_variant		ENST00000355716.5	NP_003811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF14	ENST00000355716.5 linkuse as main transcript	c.305-98G>A		intron_variant		1	NM_003820.4	ENSP00000347948	P1	Q92956-1

Frequencies

GnomAD3 genomes

AF:

0.0266

AC:

4043

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00613

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0272

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0508

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0385

Gnomad OTH

AF:

0.0229

GnomAD3 exomes

AF:

0.0247

AC:

3493

AN:

141290

Hom.:

AF XY:

0.0247

AC XY:

1890

AN XY:

76428

show subpopulations

Gnomad AFR exome

AF:

0.00409

Gnomad AMR exome

AF:

0.0167

Gnomad ASJ exome

AF:

0.0438

Gnomad EAS exome

AF:

0.000268

Gnomad SAS exome

AF:

0.00456

Gnomad FIN exome

AF:

0.0563

Gnomad NFE exome

AF:

0.0373

Gnomad OTH exome

AF:

0.0292

GnomAD4 exome

AF:

0.0332

AC:

45964

AN:

1385838

Hom.:

835

Cov.:

AF XY:

0.0326

AC XY:

22307

AN XY:

684054

show subpopulations

Gnomad4 AFR exome

AF:

0.00515

Gnomad4 AMR exome

AF:

0.0169

Gnomad4 ASJ exome

AF:

0.0414

Gnomad4 EAS exome

AF:

0.000251

Gnomad4 SAS exome

AF:

0.00457

Gnomad4 FIN exome

AF:

0.0577

Gnomad4 NFE exome

AF:

0.0370

Gnomad4 OTH exome

AF:

0.0306

GnomAD4 genome

AF:

0.0265

AC:

4042

AN:

152294

Hom.:

Cov.:

AF XY:

0.0264

AC XY:

1968

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00609

Gnomad4 AMR

AF:

0.0271

Gnomad4 ASJ

AF:

0.0375

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0508

Gnomad4 NFE

AF:

0.0385

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0342

Hom.:

Bravo

AF:

0.0241

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

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

-0.89

CADD

Benign

2.4

DANN

Benign

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over