rs4561508

Variant names:

• chr17-16945436-C-T
• rs4561508
• NM_012452.3:c.445+3302G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012452.3(TNFRSF13B):​c.445+3302G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,266 control chromosomes in the GnomAD database, including 1,355 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1355 hom., cov: 32)
• Consequence: TNFRSF13B NM_012452.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317
• 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

ENSG00000307457 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3	c.445+3302G>A		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+3302G>A		intron_variant	Intron 3 of 4	1	NM_012452.3	ENSP00000261652.2

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18868 AN: 152146 Hom.: 1355 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0975

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.113

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.124 AC: 18876 AN: 152266 Hom.: 1355 Cov.: 32 AF XY: 0.127 AC XY: 9433 AN XY: 74450

African (AFR) AF: 0.120 AC: 4994 AN: 41544

American (AMR) AF: 0.125 AC: 1915 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3472

East Asian (EAS) AF: 0.398 AC: 2060 AN: 5180

South Asian (SAS) AF: 0.155 AC: 746 AN: 4822

European-Finnish (FIN) AF: 0.0975 AC: 1034 AN: 10610

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7201 AN: 68010

Other (OTH) AF: 0.112 AC: 238 AN: 2116

Alfa AF: 0.120 Hom.: 1851

Bravo AF: 0.125

Asia WGS AF: 0.253 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.4
DANN	Benign	0.94
PhyloP100		-0.32
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: rs4561508; hg19: chr17-16848750; COSMIC: COSV55427229; COSMIC: COSV55427229;