Variant chr1-2556673-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003820.4(TNFRSF14):c.9T>C(p.Pro3=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0059 in 1,609,744 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0061 ( 45 hom. )

Consequence

TNFRSF14
NM_003820.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.07

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:

TNFRSF14-AS1 (HGNC:26966): (TNFRSF14 antisense RNA 1)

TNFRSF14-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-2556673-T-C is Benign according to our data. Variant chr1-2556673-T-C is described in ClinVar as [Benign]. Clinvar id is 787525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.07 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF14	NM_003820.4 linkuse as main transcript	c.9T>C	p.Pro3=	synonymous_variant	1/8	ENST00000355716.5	NP_003811.2
TNFRSF14-AS1	NR_037844.2 linkuse as main transcript	n.59A>G		non_coding_transcript_exon_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF14	ENST00000355716.5 linkuse as main transcript	c.9T>C	p.Pro3=	synonymous_variant	1/8	1	NM_003820.4	ENSP00000347948	P1	Q92956-1
TNFRSF14-AS1	ENST00000416860.3 linkuse as main transcript	n.79A>G		non_coding_transcript_exon_variant	2/6	2

Frequencies

GnomAD3 genomes

AF:

0.00398

AC:

605

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00496

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00670

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00411

AC:

993

AN:

241854

Hom.:

AF XY:

0.00429

AC XY:

563

AN XY:

131302

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.00147

Gnomad ASJ exome

AF:

0.00837

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00553

Gnomad FIN exome

AF:

0.000249

Gnomad NFE exome

AF:

0.00605

Gnomad OTH exome

AF:

0.00272

GnomAD4 exome

AF:

0.00610

AC:

8886

AN:

1457426

Hom.:

Cov.:

AF XY:

0.00607

AC XY:

4396

AN XY:

724580

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.00927

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00607

Gnomad4 FIN exome

AF:

0.000397

Gnomad4 NFE exome

AF:

0.00691

Gnomad4 OTH exome

AF:

0.00504

GnomAD4 genome

AF:

0.00397

AC:

605

AN:

152318

Hom.:

Cov.:

AF XY:

0.00337

AC XY:

251

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00670

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00561

Hom.:

Bravo

AF:

0.00394

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

7.5

DANN

Benign

0.50

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