NM_012452.3:c.81G>A

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.81G>A(p.Thr27Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 1,614,088 control chromosomes in the GnomAD database, including 483,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 51755 hom., cov: 33)

Exomes 𝑓: 0.77 ( 431762 hom. )

Consequence

TNFRSF13B
NM_012452.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: -1.98

Publications

27 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=-0.77).

BP6

Variant 17-16952564-C-T is Benign according to our data. Variant chr17-16952564-C-T is described in ClinVar as Benign. ClinVar VariationId is 36879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.98 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012452.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF13B	NM_012452.3	MANE Select	c.81G>A	p.Thr27Thr	synonymous	Exon 2 of 5	NP_036584.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TNFRSF13B	ENST00000261652.7	TSL:1 MANE Select	c.81G>A	p.Thr27Thr	synonymous	Exon 2 of 5	ENSP00000261652.2
TNFRSF13B	ENST00000583789.1	TSL:1	c.62-3581G>A		intron	N/A	ENSP00000462952.1
TNFRSF13B	ENST00000579315.5	TSL:3	c.81G>A	p.Thr27Thr	synonymous	Exon 2 of 4	ENSP00000464069.1

Frequencies

GnomAD3 genomes

AF:

0.819

AC:

124657

AN:

152150

Hom.:

51691

Cov.:

show subpopulations

Gnomad AFR

AF:

0.947

Gnomad AMI

AF:

0.867

Gnomad AMR

AF:

0.803

Gnomad ASJ

AF:

0.682

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.850

Gnomad FIN

AF:

0.785

Gnomad MID

AF:

0.750

Gnomad NFE

AF:

0.742

Gnomad OTH

AF:

0.795

GnomAD2 exomes

AF:

0.806

AC:

202612

AN:

251260

AF XY:

0.802

show subpopulations

Gnomad AFR exome

AF:

0.953

Gnomad AMR exome

AF:

0.842

Gnomad ASJ exome

AF:

0.712

Gnomad EAS exome

AF:

0.999

Gnomad FIN exome

AF:

0.787

Gnomad NFE exome

AF:

0.747

Gnomad OTH exome

AF:

0.775

GnomAD4 exome

AF:

0.766

AC:

1119956

AN:

1461820

Hom.:

431762

Cov.:

AF XY:

0.767

AC XY:

557826

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.953

AC:

31922

AN:

33480

American (AMR)

AF:

0.837

AC:

37424

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.709

AC:

18524

AN:

26136

East Asian (EAS)

AF:

0.999

AC:

39677

AN:

39700

South Asian (SAS)

AF:

0.840

AC:

72466

AN:

86258

European-Finnish (FIN)

AF:

0.782

AC:

41743

AN:

53408

Middle Eastern (MID)

AF:

0.747

AC:

4310

AN:

5768

European-Non Finnish (NFE)

AF:

0.744

AC:

827204

AN:

1111958

Other (OTH)

AF:

0.773

AC:

46686

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

17058

34116

51175

68233

85291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20326

40652

60978

81304

101630

<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:

0.819

AC:

124783

AN:

152268

Hom.:

51755

Cov.:

AF XY:

0.824

AC XY:

61331

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.947

AC:

39372

AN:

41562

American (AMR)

AF:

0.804

AC:

12295

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.682

AC:

2365

AN:

3470

East Asian (EAS)

AF:

0.997

AC:

5174

AN:

5188

South Asian (SAS)

AF:

0.850

AC:

4103

AN:

4826

European-Finnish (FIN)

AF:

0.785

AC:

8328

AN:

10614

Middle Eastern (MID)

AF:

0.752

AC:

221

AN:

294

European-Non Finnish (NFE)

AF:

0.742

AC:

50448

AN:

67986

Other (OTH)

AF:

0.797

AC:

1686

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1144

2288

3433

4577

5721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

876

1752

2628

3504

4380

<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:

0.771

Hom.:

139377

Bravo

AF:

0.825

Asia WGS

AF:

0.928

AC:

3229

AN:

3478

EpiCase

AF:

0.743

EpiControl

AF:

0.739

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 94. Only high quality variants are reported.

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Immunodeficiency, common variable, 2

Benign:3

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Aug 18, 2011

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing;curation

not provided

Benign:2Other:1

Nov 25, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing.

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Common Variable Immune Deficiency, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.0

(source)

DANN

Benign

0.55

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over