Variant rs17568 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003327.4(TNFRSF4):c.534G>A(p.Glu178=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,611,028 control chromosomes in the GnomAD database, including 76,346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 9219 hom., cov: 34)

Exomes 𝑓: 0.27 ( 67127 hom. )

Consequence

TNFRSF4
NM_003327.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.00300

Variant links:

Genes affected

TNFRSF4 (HGNC:11918): (TNF receptor superfamily member 4) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor has been shown to activate NF-kappaB through its interaction with adaptor proteins TRAF2 and TRAF5. Knockout studies in mice suggested that this receptor promotes the expression of apoptosis inhibitors BCL2 and BCL2lL1/BCL2-XL, and thus suppresses apoptosis. The knockout studies also suggested the roles of this receptor in CD4+ T cell response, as well as in T cell-dependent B cell proliferation and differentiation. [provided by RefSeq, Jul 2008]

TNFRSF4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 1-1212042-C-T is Benign according to our data. Variant chr1-1212042-C-T is described in ClinVar as [Benign]. Clinvar id is 403556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.003 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF4	NM_003327.4 linkuse as main transcript	c.534G>A	p.Glu178=	synonymous_variant	5/7	ENST00000379236.4	NP_003318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF4	ENST00000379236.4 linkuse as main transcript	c.534G>A	p.Glu178=	synonymous_variant	5/7	1	NM_003327.4	ENSP00000368538	P1

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48124

AN:

151944

Hom.:

9189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.751

Gnomad SAS

AF:

0.580

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.301

GnomAD3 exomes

AF:

0.367

AC:

89404

AN:

243526

Hom.:

21552

AF XY:

0.360

AC XY:

47843

AN XY:

132802

show subpopulations

Gnomad AFR exome

AF:

0.396

Gnomad AMR exome

AF:

0.623

Gnomad ASJ exome

AF:

0.182

Gnomad EAS exome

AF:

0.742

Gnomad SAS exome

AF:

0.565

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.212

Gnomad OTH exome

AF:

0.304

GnomAD4 exome

AF:

0.268

AC:

391246

AN:

1458966

Hom.:

67127

Cov.:

AF XY:

0.275

AC XY:

199321

AN XY:

725776

show subpopulations

Gnomad4 AFR exome

AF:

0.403

Gnomad4 AMR exome

AF:

0.602

Gnomad4 ASJ exome

AF:

0.186

Gnomad4 EAS exome

AF:

0.768

Gnomad4 SAS exome

AF:

0.556

Gnomad4 FIN exome

AF:

0.232

Gnomad4 NFE exome

AF:

0.212

Gnomad4 OTH exome

AF:

0.298

GnomAD4 genome

AF:

0.317

AC:

48202

AN:

152062

Hom.:

9219

Cov.:

AF XY:

0.326

AC XY:

24241

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.394

Gnomad4 AMR

AF:

0.460

Gnomad4 ASJ

AF:

0.190

Gnomad4 EAS

AF:

0.751

Gnomad4 SAS

AF:

0.580

Gnomad4 FIN

AF:

0.224

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.310

Alfa

AF:

0.241

Hom.:

2251

Bravo

AF:

0.332

Asia WGS

AF:

0.682

AC:

2366

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Combined immunodeficiency due to OX40 deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.6

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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