17-16939677-G-A

Position:

chr17-16939677-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012452.3(TNFRSF13B):c.752C>T(p.Pro251Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,610,656 control chromosomes in the GnomAD database, including 13,192 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P251S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.13 ( 1409 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11783 hom. )

Consequence

TNFRSF13B
NM_012452.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.825

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022192597).

BP6

Variant 17-16939677-G-A is Benign according to our data. Variant chr17-16939677-G-A is described in ClinVar as [Benign]. Clinvar id is 322025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF13B	NM_012452.3 linkuse as main transcript	c.752C>T	p.Pro251Leu	missense_variant	5/5	ENST00000261652.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF13B	ENST00000261652.7 linkuse as main transcript	c.752C>T	p.Pro251Leu	missense_variant	5/5	1	NM_012452.3	P2	O14836-1

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

19408

AN:

152080

Hom.:

1411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.403

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.0987

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.112

GnomAD3 exomes

AF:

0.139

AC:

34438

AN:

248042

Hom.:

3182

AF XY:

0.140

AC XY:

18731

AN XY:

134252

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.102

Gnomad ASJ exome

AF:

0.140

Gnomad EAS exome

AF:

0.406

Gnomad SAS exome

AF:

0.160

Gnomad FIN exome

AF:

0.0991

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.121

GnomAD4 exome

AF:

0.115

AC:

168414

AN:

1458458

Hom.:

11783

Cov.:

AF XY:

0.117

AC XY:

85143

AN XY:

724934

show subpopulations

Gnomad4 AFR exome

AF:

0.135

Gnomad4 AMR exome

AF:

0.103

Gnomad4 ASJ exome

AF:

0.139

Gnomad4 EAS exome

AF:

0.382

Gnomad4 SAS exome

AF:

0.160

Gnomad4 FIN exome

AF:

0.0972

Gnomad4 NFE exome

AF:

0.102

Gnomad4 OTH exome

AF:

0.130

GnomAD4 genome

AF:

0.128

AC:

19407

AN:

152198

Hom.:

1409

Cov.:

AF XY:

0.130

AC XY:

9708

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.122

Gnomad4 ASJ

AF:

0.140

Gnomad4 EAS

AF:

0.403

Gnomad4 SAS

AF:

0.156

Gnomad4 FIN

AF:

0.0987

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.111

Alfa

AF:

0.120

Hom.:

1966

Bravo

AF:

0.129

TwinsUK

AF:

0.104

AC:

384

ALSPAC

AF:

0.0981

AC:

378

ESP6500AA

AF:

0.134

AC:

589

ESP6500EA

AF:

0.110

AC:

945

ExAC

AF:

0.139

AC:

16847

Asia WGS

AF:

0.249

AC:

867

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 29% of patients studied by a panel of primary immunodeficiencies. Number of patients: 28. Only high quality variants are reported. -
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 -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 28728263) -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 04, 2019	- -

Immunodeficiency, common variable, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

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

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.56

T;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.8

N;.

REVEL

Benign

0.26

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.73

P;P

Vest4

0.049

MPC

0.013

ClinPred

0.015

GERP RS

0.88

Varity_R

0.022

gMVP

0.074

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