rs11652811

Variant names:

• chr17-16939857-A-G
• rs11652811
• NM_012452.3:c.632-60T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012452.3(TNFRSF13B):​c.632-60T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,545,782 control chromosomes in the GnomAD database, including 47,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3381 hom., cov: 33)
  • Exomes 𝑓: 0.24 (44410 hom.)
• Consequence: TNFRSF13B NM_012452.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.222
• Publications: 8 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

ENSG00000307457 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-16939857-A-G is Benign according to our data. Variant chr17-16939857-A-G is described in ClinVar as Benign. ClinVar VariationId is 2688220.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3	c.632-60T>C		intron_variant	Intron 4 of 4	ENST00000261652.7	NP_036584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF13B	ENST00000261652.7	c.632-60T>C		intron_variant	Intron 4 of 4	1	NM_012452.3	ENSP00000261652.2

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28559 AN: 151982 Hom.: 3383 Cov.: 33

Gnomad AFR AF: 0.0552

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.244 AC: 339890 AN: 1393684 Hom.: 44410 Cov.: 33 AF XY: 0.243 AC XY: 166433 AN XY: 686218

African (AFR) AF: 0.0474 AC: 1509 AN: 31814

American (AMR) AF: 0.168 AC: 6261 AN: 37162

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 6764 AN: 22886

East Asian (EAS) AF: 0.000597 AC: 23 AN: 38512

South Asian (SAS) AF: 0.158 AC: 12120 AN: 76764

European-Finnish (FIN) AF: 0.218 AC: 9979 AN: 45742

Middle Eastern (MID) AF: 0.272 AC: 1098 AN: 4032

European-Non Finnish (NFE) AF: 0.267 AC: 288644 AN: 1079394

Other (OTH) AF: 0.235 AC: 13492 AN: 57378

GnomAD4 genome AF: 0.188 AC: 28553 AN: 152098 Hom.: 3381 Cov.: 33 AF XY: 0.183 AC XY: 13576 AN XY: 74352

African (AFR) AF: 0.0550 AC: 2284 AN: 41516

American (AMR) AF: 0.208 AC: 3186 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1119 AN: 3470

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5170

South Asian (SAS) AF: 0.149 AC: 720 AN: 4818

European-Finnish (FIN) AF: 0.217 AC: 2304 AN: 10602

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18266 AN: 67922

Other (OTH) AF: 0.212 AC: 449 AN: 2114

Alfa AF: 0.224 Hom.: 520

Bravo AF: 0.182

Asia WGS AF: 0.0730 AC: 254 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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 33% of patients studied by a panel of primary immunodeficiencies. Number of patients: 31. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.3
DANN	Benign	0.36
PhyloP100		0.22
Mutation Taster		=100/0	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: rs11652811; hg19: chr17-16843171;