Variant rs2298212 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003327.4(TNFRSF4):c.634+25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 1,517,954 control chromosomes in the GnomAD database, including 6,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.081 ( 595 hom., cov: 33)

Exomes 𝑓: 0.092 ( 6068 hom. )

Consequence

TNFRSF4
NM_003327.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.135

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-1211917-G-A is Benign according to our data. Variant chr1-1211917-G-A is described in ClinVar as [Benign]. Clinvar id is 1168340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF4	NM_003327.4 linkuse as main transcript	c.634+25C>T		intron_variant		ENST00000379236.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF4	ENST00000379236.4 linkuse as main transcript	c.634+25C>T		intron_variant		1	NM_003327.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0811

AC:

12336

AN:

152026

Hom.:

594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0620

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.0541

Gnomad ASJ

AF:

0.0718

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.0834

Gnomad FIN

AF:

0.0924

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0925

Gnomad OTH

AF:

0.0728

GnomAD3 exomes

AF:

0.0834

AC:

10924

AN:

130920

Hom.:

507

AF XY:

0.0839

AC XY:

5994

AN XY:

71404

show subpopulations

Gnomad AFR exome

AF:

0.0627

Gnomad AMR exome

AF:

0.0460

Gnomad ASJ exome

AF:

0.0694

Gnomad EAS exome

AF:

0.144

Gnomad SAS exome

AF:

0.0755

Gnomad FIN exome

AF:

0.0956

Gnomad NFE exome

AF:

0.0890

Gnomad OTH exome

AF:

0.0836

GnomAD4 exome

AF:

0.0916

AC:

125046

AN:

1365812

Hom.:

6068

Cov.:

AF XY:

0.0911

AC XY:

61232

AN XY:

672032

show subpopulations

Gnomad4 AFR exome

AF:

0.0617

Gnomad4 AMR exome

AF:

0.0481

Gnomad4 ASJ exome

AF:

0.0704

Gnomad4 EAS exome

AF:

0.146

Gnomad4 SAS exome

AF:

0.0813

Gnomad4 FIN exome

AF:

0.0957

Gnomad4 NFE exome

AF:

0.0928

Gnomad4 OTH exome

AF:

0.0925

GnomAD4 genome

AF:

0.0811

AC:

12335

AN:

152142

Hom.:

595

Cov.:

AF XY:

0.0821

AC XY:

6108

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0620

Gnomad4 AMR

AF:

0.0540

Gnomad4 ASJ

AF:

0.0718

Gnomad4 EAS

AF:

0.148

Gnomad4 SAS

AF:

0.0824

Gnomad4 FIN

AF:

0.0924

Gnomad4 NFE

AF:

0.0924

Gnomad4 OTH

AF:

0.0716

Alfa

AF:

0.0883

Hom.:

125

Bravo

AF:

0.0786

Asia WGS

AF:

0.102

AC:

357

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Combined immunodeficiency due to OX40 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 11, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

This variant is associated with the following publications: (PMID: 16329997) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.7

DANN

Benign

0.45

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