Variant 17-16952564-C-T 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.81G>A(p.Thr27=) 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

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=-0.77).

BP6

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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3 linkuse as main transcript	c.81G>A	p.Thr27=	synonymous_variant	2/5	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.81G>A	p.Thr27=	synonymous_variant	2/5	1	NM_012452.3	ENSP00000261652	P2	O14836-1

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

GnomAD3 exomes

AF:

0.806

AC:

202612

AN:

251260

Hom.:

82601

AF XY:

0.802

AC XY:

108905

AN XY:

135806

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 SAS exome

AF:

0.845

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

Gnomad4 AFR exome

AF:

0.953

Gnomad4 AMR exome

AF:

0.837

Gnomad4 ASJ exome

AF:

0.709

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.840

Gnomad4 FIN exome

AF:

0.782

Gnomad4 NFE exome

AF:

0.744

Gnomad4 OTH exome

AF:

0.773

GnomAD4 genome

AF:

0.819

AC:

124783

AN:

152268

Hom.:

51755

Cov.:

AF XY:

0.824

AC XY:

61331

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.947

Gnomad4 AMR

AF:

0.804

Gnomad4 ASJ

AF:

0.682

Gnomad4 EAS

AF:

0.997

Gnomad4 SAS

AF:

0.850

Gnomad4 FIN

AF:

0.785

Gnomad4 NFE

AF:

0.742

Gnomad4 OTH

AF:

0.797

Alfa

AF:

0.758

Hom.:

89825

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

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	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 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 94. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Immunodeficiency, common variable, 2

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing;curation	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 18, 2011	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

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

-0.77

CADD

Benign

1.0

DANN

Benign

0.55

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

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