17-16939598-A-G

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.831T>C(p.Ser277Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,612,726 control chromosomes in the GnomAD database, including 168,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19706 hom., cov: 31)

Exomes 𝑓: 0.44 ( 149108 hom. )

Consequence

TNFRSF13B
NM_012452.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: -0.875

Publications

25 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:

ENSG00000307457 (HGNC:):

ENSG00000307457 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=-0.96).

BP6

Variant 17-16939598-A-G is Benign according to our data. Variant chr17-16939598-A-G is described in ClinVar as Benign. ClinVar VariationId is 260259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.875 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3 link	c.831T>C	p.Ser277Ser	synonymous_variant	Exon 5 of 5	ENST00000261652.7	NP_036584.1	O14836-1Q4ACX1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF13B	ENST00000261652.7 link	c.831T>C	p.Ser277Ser	synonymous_variant	Exon 5 of 5	1	NM_012452.3	ENSP00000261652.2		O14836-1

Frequencies

GnomAD3 genomes

AF:

0.495

AC:

75120

AN:

151718

Hom.:

19662

Cov.:

show subpopulations

Gnomad AFR

AF:

0.612

Gnomad AMI

AF:

0.376

Gnomad AMR

AF:

0.540

Gnomad ASJ

AF:

0.463

Gnomad EAS

AF:

0.809

Gnomad SAS

AF:

0.609

Gnomad FIN

AF:

0.355

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.463

GnomAD2 exomes

AF:

0.495

AC:

122856

AN:

248314

AF XY:

0.492

show subpopulations

Gnomad AFR exome

AF:

0.616

Gnomad AMR exome

AF:

0.564

Gnomad ASJ exome

AF:

0.454

Gnomad EAS exome

AF:

0.798

Gnomad FIN exome

AF:

0.353

Gnomad NFE exome

AF:

0.405

Gnomad OTH exome

AF:

0.466

GnomAD4 exome

AF:

0.442

AC:

645265

AN:

1460890

Hom.:

149108

Cov.:

AF XY:

0.446

AC XY:

324418

AN XY:

726644

show subpopulations

African (AFR)

AF:

0.622

AC:

20818

AN:

33468

American (AMR)

AF:

0.559

AC:

24915

AN:

44598

Ashkenazi Jewish (ASJ)

AF:

0.453

AC:

11833

AN:

26100

East Asian (EAS)

AF:

0.830

AC:

32922

AN:

39680

South Asian (SAS)

AF:

0.611

AC:

52584

AN:

86102

European-Finnish (FIN)

AF:

0.358

AC:

19128

AN:

53404

Middle Eastern (MID)

AF:

0.516

AC:

2971

AN:

5760

European-Non Finnish (NFE)

AF:

0.406

AC:

451534

AN:

1111436

Other (OTH)

AF:

0.473

AC:

28560

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

19705

39410

59114

78819

98524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14268

28536

42804

57072

71340

<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:

0.495

AC:

75222

AN:

151836

Hom.:

19706

Cov.:

AF XY:

0.499

AC XY:

36977

AN XY:

74172

show subpopulations

African (AFR)

AF:

0.612

AC:

25329

AN:

41386

American (AMR)

AF:

0.540

AC:

8260

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.463

AC:

1603

AN:

3464

East Asian (EAS)

AF:

0.810

AC:

4155

AN:

5132

South Asian (SAS)

AF:

0.610

AC:

2937

AN:

4812

European-Finnish (FIN)

AF:

0.355

AC:

3742

AN:

10536

Middle Eastern (MID)

AF:

0.462

AC:

134

AN:

290

European-Non Finnish (NFE)

AF:

0.408

AC:

27738

AN:

67906

Other (OTH)

AF:

0.466

AC:

983

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1854

3708

5561

7415

9269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

670

1340

2010

2680

3350

<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:

0.437

Hom.:

20236

Bravo

AF:

0.514

Asia WGS

AF:

0.708

AC:

2461

AN:

3478

EpiCase

AF:

0.416

EpiControl

AF:

0.417

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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 68% of patients studied by a panel of primary immunodeficiencies. Number of patients: 65. Only high quality variants are reported. -

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:2Other:1

Nov 04, 2019

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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. -

Immunodeficiency, common variable, 2

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 10, 2021

Genome-Nilou Lab

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: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

-0.96

CADD

Benign

0.53

(source)

DANN

Benign

0.37

PhyloP100

-0.88

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