Variant 17-16939598-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012452.3(TNFRSF13B):c.831T>C(p.Ser277=) 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 260259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-16939598-A-G is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3 linkuse as main transcript	c.831T>C	p.Ser277=	synonymous_variant	5/5	ENST00000261652.7	NP_036584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF13B	ENST00000261652.7 linkuse as main transcript	c.831T>C	p.Ser277=	synonymous_variant	5/5	1	NM_012452.3	ENSP00000261652	P2	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

GnomAD3 exomes

AF:

0.495

AC:

122856

AN:

248314

Hom.:

32451

AF XY:

0.492

AC XY:

66151

AN XY:

134406

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 SAS exome

AF:

0.615

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

Gnomad4 AFR exome

AF:

0.622

Gnomad4 AMR exome

AF:

0.559

Gnomad4 ASJ exome

AF:

0.453

Gnomad4 EAS exome

AF:

0.830

Gnomad4 SAS exome

AF:

0.611

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.406

Gnomad4 OTH exome

AF:

0.473

GnomAD4 genome

AF:

0.495

AC:

75222

AN:

151836

Hom.:

19706

Cov.:

AF XY:

0.499

AC XY:

36977

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.612

Gnomad4 AMR

AF:

0.540

Gnomad4 ASJ

AF:

0.463

Gnomad4 EAS

AF:

0.810

Gnomad4 SAS

AF:

0.610

Gnomad4 FIN

AF:

0.355

Gnomad4 NFE

AF:

0.408

Gnomad4 OTH

AF:

0.466

Alfa

AF:

0.435

Hom.:

17351

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

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	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 -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	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. -

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 04, 2019	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -

Common Variable Immune Deficiency, Dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.53

DANN

Benign

0.37

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