rs4985726

Variant names:

• chr17-16960324-C-G
• rs4985726
• NM_012452.3:c.62-7741G>C

Variant summary

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

The NM_012452.3(TNFRSF13B):​c.62-7741G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,146 control chromosomes in the GnomAD database, including 1,182 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 0.11 (1182 hom., cov: 32)
• Consequence: TNFRSF13B NM_012452.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265
• Publications: 18 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3	c.62-7741G>C		intron_variant	Intron 1 of 4	ENST00000261652.7	NP_036584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF13B	ENST00000261652.7	c.62-7741G>C		intron_variant	Intron 1 of 4	1	NM_012452.3	ENSP00000261652.2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16926 AN: 152028 Hom.: 1186 Cov.: 32

Gnomad AFR AF: 0.0757

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0979

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.111 AC: 16920 AN: 152146 Hom.: 1182 Cov.: 32 AF XY: 0.115 AC XY: 8522 AN XY: 74400

African (AFR) AF: 0.0755 AC: 3135 AN: 41522

American (AMR) AF: 0.119 AC: 1818 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3464

East Asian (EAS) AF: 0.400 AC: 2069 AN: 5178

South Asian (SAS) AF: 0.155 AC: 747 AN: 4822

European-Finnish (FIN) AF: 0.0979 AC: 1037 AN: 10592

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7195 AN: 67966

Other (OTH) AF: 0.103 AC: 217 AN: 2108

Alfa AF: 0.119 Hom.: 712

Bravo AF: 0.111

Asia WGS AF: 0.247 AC: 858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.58
PhyloP100		0.27
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: rs4985726; hg19: chr17-16863638;