rs4792800

chr17-16941853-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012452.3(TNFRSF13B):c.446-1342T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,132 control chromosomes in the GnomAD database, including 1,454 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 0.13 (1454 hom., cov: 32)
• Consequence: TNFRSF13B NM_012452.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF13B	NM_012452.3	c.446-1342T>C		intron_variant		ENST00000261652.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF13B	ENST00000261652.7	c.446-1342T>C		intron_variant		1	NM_012452.3	P2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19436 AN: 152014 Hom.: 1457 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.128 AC: 19431 AN: 152132 Hom.: 1454 Cov.: 32 AF XY: 0.130 AC XY: 9702 AN XY: 74368

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.0991

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.115

Alfa AF: 0.120 Hom.: 1981

Bravo AF: 0.129

Asia WGS AF: 0.259 AC: 900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.57
Dann	Benign	0.59

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: rs4792800; hg19: chr17-16845167; COSMIC: COSV55427160; COSMIC: COSV55427160;