Variant 1-1211644-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003327.4(TNFRSF4):c.764-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00719 in 1,563,318 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0074 ( 48 hom. )

Consequence

TNFRSF4
NM_003327.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.251

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 1-1211644-G-A is Benign according to our data. Variant chr1-1211644-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1168816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF4	NM_003327.4 linkuse as main transcript	c.764-19C>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.764-19C>T		intron_variant		1	NM_003327.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00555

AC:

844

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00205

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.00752

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00802

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00488

AC:

998

AN:

204708

Hom.:

AF XY:

0.00496

AC XY:

558

AN XY:

112572

show subpopulations

Gnomad AFR exome

AF:

0.00252

Gnomad AMR exome

AF:

0.00447

Gnomad ASJ exome

AF:

0.00158

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00254

Gnomad FIN exome

AF:

0.00260

Gnomad NFE exome

AF:

0.00738

Gnomad OTH exome

AF:

0.00665

GnomAD4 exome

AF:

0.00737

AC:

10395

AN:

1411066

Hom.:

Cov.:

AF XY:

0.00721

AC XY:

5037

AN XY:

698526

show subpopulations

Gnomad4 AFR exome

AF:

0.00127

Gnomad4 AMR exome

AF:

0.00417

Gnomad4 ASJ exome

AF:

0.00171

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00266

Gnomad4 FIN exome

AF:

0.00302

Gnomad4 NFE exome

AF:

0.00865

Gnomad4 OTH exome

AF:

0.00630

GnomAD4 genome

AF:

0.00554

AC:

844

AN:

152252

Hom.:

Cov.:

AF XY:

0.00525

AC XY:

391

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00205

Gnomad4 AMR

AF:

0.00751

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00802

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00345

Hom.:

Bravo

AF:

0.00596

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	TNFRSF4: BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Combined immunodeficiency due to OX40 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.0

DANN

Benign

0.62

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