dbSNP rs2298209: TNFRSF4:c.*150C>G (chr1-1211405-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003327.4(TNFRSF4):c.*150C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 702,290 control chromosomes in the GnomAD database, including 426 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.019 ( 55 hom., cov: 33)

Exomes 𝑓: 0.024 ( 371 hom. )

Consequence

TNFRSF4
NM_003327.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.41

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

combined immunodeficiency due to OX40 deficiency
Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, PanelApp Australia

TNFRSF4 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_003327.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0956 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003327.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF4	NM_003327.4	MANE Select	c.*150C>G		3_prime_UTR	Exon 7 of 7	NP_003318.1	P43489
	TNFRSF4	NM_001410709.1		c.*150C>G		3_prime_UTR	Exon 6 of 6	NP_001397638.1	A0A8V8TQH5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNFRSF4	ENST00000379236.4	TSL:1 MANE Select	c.*150C>G	3_prime_UTR	Exon 7 of 7	ENSP00000368538.3	P43489
TNFRSF4	ENST00000699971.1		c.*25C>G	3_prime_UTR	Exon 6 of 6	ENSP00000514728.1	A0A8V8TP52
TNFRSF4	ENST00000699974.1		c.*150C>G	3_prime_UTR	Exon 6 of 6	ENSP00000514730.1	A0A8V8TQH5

Frequencies

GnomAD3 genomes

AF:

0.0190

AC:

2899

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.0356

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0160

Gnomad OTH

AF:

0.0201

GnomAD4 exome

AF:

0.0239

AC:

13130

AN:

549944

Hom.:

371

Cov.:

AF XY:

0.0231

AC XY:

6409

AN XY:

276926

show subpopulations

African (AFR)

AF:

0.0128

AC:

148

AN:

11582

American (AMR)

AF:

0.0148

AC:

169

AN:

11452

Ashkenazi Jewish (ASJ)

AF:

0.00469

AC:

AN:

12576

East Asian (EAS)

AF:

0.134

AC:

3362

AN:

25144

South Asian (SAS)

AF:

0.0117

AC:

331

AN:

28396

European-Finnish (FIN)

AF:

0.0422

AC:

1434

AN:

33964

Middle Eastern (MID)

AF:

0.00378

AC:

AN:

2116

European-Non Finnish (NFE)

AF:

0.0174

AC:

6909

AN:

396842

Other (OTH)

AF:

0.0255

AC:

710

AN:

27872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

674

1349

2023

2698

3372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

220

440

660

880

1100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0190

AC:

2899

AN:

152346

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

1470

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0142

AC:

591

AN:

41590

American (AMR)

AF:

0.0125

AC:

191

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3470

East Asian (EAS)

AF:

0.103

AC:

530

AN:

5154

South Asian (SAS)

AF:

0.0124

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0356

AC:

379

AN:

10632

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0160

AC:

1088

AN:

68038

Other (OTH)

AF:

0.0198

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

155

310

465

620

775

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0185

Hom.:

Bravo

AF:

0.0174

Asia WGS

AF:

0.0610

AC:

211

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.9

(source)

DANN

Benign

0.66

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over