rs11652811

chr17-16939857-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
TNFRSF13B	NM_012452.3	c.632-60T>C		intron_variant		ENST00000261652.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF13B	ENST00000261652.7	c.632-60T>C		intron_variant		1	NM_012452.3	P2

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

Gnomad4 AFR exome AF: 0.0474

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.000597

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.235

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

Gnomad4 AFR AF: 0.0550

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.212

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

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 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

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

Other links and lift over

dbSNP: rs11652811; hg19: chr17-16843171;