rs35062843

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012452.3(TNFRSF13B):c.291T>G(p.Pro97Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0412 in 1,614,174 control chromosomes in the GnomAD database, including 1,679 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 125 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1554 hom. )

Consequence

TNFRSF13B
NM_012452.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.313

Publications

10 publications found

Variant links:

Genes affected

TNFRSF13B (HGNC:18153): (TNF receptor superfamily member 13B) The protein encoded by this gene is a lymphocyte-specific member of the tumor necrosis factor (TNF) receptor superfamily. It interacts with calcium-modulator and cyclophilin ligand (CAML). The protein induces activation of the transcription factors NFAT, AP1, and NF-kappa-B and plays a crucial role in humoral immunity by interacting with a TNF ligand. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

TNFRSF13B Gene-Disease associations (from GenCC):

immunodeficiency, common variable, 2
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen, G2P, Ambry Genetics
common variable immunodeficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TNFRSF13B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-16948892-A-C is Benign according to our data. Variant chr17-16948892-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.313 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3 link	c.291T>G	p.Pro97Pro	synonymous_variant	Exon 3 of 5	ENST00000261652.7	NP_036584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF13B	ENST00000261652.7 link	c.291T>G	p.Pro97Pro	synonymous_variant	Exon 3 of 5	1	NM_012452.3	ENSP00000261652.2

Frequencies

GnomAD3 genomes

AF:

0.0365

AC:

5561

AN:

152176

Hom.:

121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0246

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0551

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00943

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.0331

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0383

Gnomad OTH

AF:

0.0483

GnomAD2 exomes

AF:

0.0415

AC:

10448

AN:

251480

AF XY:

0.0443

show subpopulations

Gnomad AFR exome

AF:

0.0239

Gnomad AMR exome

AF:

0.0383

Gnomad ASJ exome

AF:

0.0115

Gnomad EAS exome

AF:

0.00799

Gnomad FIN exome

AF:

0.0375

Gnomad NFE exome

AF:

0.0373

Gnomad OTH exome

AF:

0.0401

GnomAD4 exome

AF:

0.0417

AC:

61000

AN:

1461880

Hom.:

1554

Cov.:

AF XY:

0.0434

AC XY:

31551

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.0251

AC:

839

AN:

33480

American (AMR)

AF:

0.0411

AC:

1837

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

288

AN:

26136

East Asian (EAS)

AF:

0.00851

AC:

338

AN:

39700

South Asian (SAS)

AF:

0.100

AC:

8652

AN:

86256

European-Finnish (FIN)

AF:

0.0385

AC:

2055

AN:

53418

Middle Eastern (MID)

AF:

0.0335

AC:

193

AN:

5768

European-Non Finnish (NFE)

AF:

0.0398

AC:

44275

AN:

1112002

Other (OTH)

AF:

0.0418

AC:

2523

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

3710

7421

11131

14842

18552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1732

3464

5196

6928

8660

<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:

0.0366

AC:

5572

AN:

152294

Hom.:

125

Cov.:

AF XY:

0.0375

AC XY:

2795

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0245

AC:

1019

AN:

41572

American (AMR)

AF:

0.0551

AC:

842

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

AN:

3472

East Asian (EAS)

AF:

0.00946

AC:

AN:

5182

South Asian (SAS)

AF:

0.104

AC:

501

AN:

4818

European-Finnish (FIN)

AF:

0.0331

AC:

351

AN:

10610

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0383

AC:

2605

AN:

68032

Other (OTH)

AF:

0.0544

AC:

115

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

279

558

838

1117

1396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0349

Hom.:

Bravo

AF:

0.0342

Asia WGS

AF:

0.0990

AC:

344

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 11, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Immunodeficiency, common variable, 2

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Common Variable Immune Deficiency, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

9.0

(source)

DANN

Benign

0.56

PhyloP100

-0.31

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over