Variant 17-16948713-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012452.3(TNFRSF13B):c.445+25A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,612,792 control chromosomes in the GnomAD database, including 117,095 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10508 hom., cov: 32)

Exomes 𝑓: 0.38 ( 106587 hom. )

Consequence

TNFRSF13B
NM_012452.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.85

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:

TNFRSF13B (HGNC:):

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 (BayesDel_noAF=-0.84).

BP6

Variant 17-16948713-T-G is Benign according to our data. Variant chr17-16948713-T-G is described in ClinVar as [Benign]. Clinvar id is 440341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 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.445+25A>C		intron_variant		ENST00000261652.7	NP_036584.1	O14836-1Q4ACX1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF13B	ENST00000261652.7 linkuse as main transcript	c.445+25A>C		intron_variant		1	NM_012452.3	ENSP00000261652.2		O14836-1

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55364

AN:

151982

Hom.:

10504

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.653

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.373

Gnomad OTH

AF:

0.368

GnomAD3 exomes

AF:

0.394

AC:

98907

AN:

251334

Hom.:

20467

AF XY:

0.395

AC XY:

53705

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.297

Gnomad AMR exome

AF:

0.375

Gnomad ASJ exome

AF:

0.472

Gnomad EAS exome

AF:

0.661

Gnomad SAS exome

AF:

0.402

Gnomad FIN exome

AF:

0.329

Gnomad NFE exome

AF:

0.372

Gnomad OTH exome

AF:

0.399

GnomAD4 exome

AF:

0.378

AC:

551425

AN:

1460692

Hom.:

106587

Cov.:

AF XY:

0.380

AC XY:

275871

AN XY:

726678

show subpopulations

Gnomad4 AFR exome

AF:

0.289

Gnomad4 AMR exome

AF:

0.376

Gnomad4 ASJ exome

AF:

0.474

Gnomad4 EAS exome

AF:

0.645

Gnomad4 SAS exome

AF:

0.403

Gnomad4 FIN exome

AF:

0.333

Gnomad4 NFE exome

AF:

0.367

Gnomad4 OTH exome

AF:

0.399

GnomAD4 genome

AF:

0.364

AC:

55403

AN:

152100

Hom.:

10508

Cov.:

AF XY:

0.365

AC XY:

27108

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.296

Gnomad4 AMR

AF:

0.392

Gnomad4 ASJ

AF:

0.500

Gnomad4 EAS

AF:

0.653

Gnomad4 SAS

AF:

0.401

Gnomad4 FIN

AF:

0.331

Gnomad4 NFE

AF:

0.373

Gnomad4 OTH

AF:

0.365

Alfa

AF:

0.383

Hom.:

19978

Bravo

AF:

0.368

Asia WGS

AF:

0.489

AC:

1701

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 04, 2019	- -

not specified

Benign:1

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 63% of patients studied by a panel of primary immunodeficiencies. Number of patients: 60. Only high quality variants are reported. -

Immunodeficiency, common variable, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.045

DANN

Benign

0.60

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