chr17-16948713-T-G

Variant names:

• chr17-16948713-T-G
• rs2274892
• NM_012452.3:c.445+25A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.85
• Publications: 17 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 CliVar as Benign. Clinvar id is 440341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-16948713-T-G is described in CliVar as Benign. Clinvar id is 440341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-16948713-T-G is described in CliVar as Benign. Clinvar id is 440341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-16948713-T-G is described in CliVar 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 rank	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3	c.445+25A>C		intron_variant	Intron 3 of 4	ENST00000261652.7	NP_036584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF13B	ENST00000261652.7	c.445+25A>C		intron_variant	Intron 3 of 4	1	NM_012452.3	ENSP00000261652.2

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55364 AN: 151982 Hom.: 10504 Cov.: 32

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

GnomAD2 exomes AF: 0.394 AC: 98907 AN: 251334 AF XY: 0.395

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 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.: 46 AF XY: 0.380 AC XY: 275871 AN XY: 726678

African (AFR) AF: 0.289 AC: 9681 AN: 33442

American (AMR) AF: 0.376 AC: 16836 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 12386 AN: 26136

East Asian (EAS) AF: 0.645 AC: 25598 AN: 39692

South Asian (SAS) AF: 0.403 AC: 34742 AN: 86158

European-Finnish (FIN) AF: 0.333 AC: 17767 AN: 53382

Middle Eastern (MID) AF: 0.463 AC: 2303 AN: 4974

European-Non Finnish (NFE) AF: 0.367 AC: 408080 AN: 1111902

Other (OTH) AF: 0.399 AC: 24032 AN: 60286

GnomAD4 genome AF: 0.364 AC: 55403 AN: 152100 Hom.: 10508 Cov.: 32 AF XY: 0.365 AC XY: 27108 AN XY: 74348

African (AFR) AF: 0.296 AC: 12268 AN: 41482

American (AMR) AF: 0.392 AC: 5994 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1736 AN: 3472

East Asian (EAS) AF: 0.653 AC: 3377 AN: 5170

South Asian (SAS) AF: 0.401 AC: 1932 AN: 4822

European-Finnish (FIN) AF: 0.331 AC: 3506 AN: 10586

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25376 AN: 67976

Other (OTH) AF: 0.365 AC: 770 AN: 2112

Alfa AF: 0.375 Hom.: 30467

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

Submissions by phenotype

not provided Benign:3

Nov 12, 2018

GeneDx

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

- -

Nov 04, 2019

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

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 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

Sep 10, 2021

Genome-Nilou Lab

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	-0.84
CADD	Benign	0.045
DANN	Benign	0.60
PhyloP100		-2.9
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2274892; hg19: chr17-16852027; COSMIC: COSV55427059;