rs4561508

Positions:

• chr17-16945436-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3	c.445+3302G>A		intron_variant		ENST00000261652.7	NP_036584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF13B	ENST00000261652.7	c.445+3302G>A		intron_variant		1	NM_012452.3	ENSP00000261652	P2

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

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0975

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.112

Alfa AF: 0.122 Hom.: 223

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

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: rs4561508; hg19: chr17-16848750; COSMIC: COSV55427229; COSMIC: COSV55427229;