17-16945825-A-G

Position:

• chr17-16945825-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.445+2913T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 151,696 control chromosomes in the GnomAD database, including 1,730 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 (1730 hom., cov: 32)
• Consequence: TNFRSF13B NM_012452.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3	c.445+2913T>C		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+2913T>C		intron_variant		1	NM_012452.3	ENSP00000261652.2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20345 AN: 151578 Hom.: 1726 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0969

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0992

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.134 AC: 20364 AN: 151696 Hom.: 1730 Cov.: 32 AF XY: 0.139 AC XY: 10312 AN XY: 74150

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.0969

Gnomad4 NFE AF: 0.0992

Gnomad4 OTH AF: 0.120

Alfa AF: 0.119 Hom.: 1939

Bravo AF: 0.142

Asia WGS AF: 0.297 AC: 1035 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	4.1
DANN	Benign	0.53

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: rs4273077; hg19: chr17-16849139;