rs17499386

Positions:

• chr13-108284965-T-C

Variant summary

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

The ENST00000375887.9(TNFSF13B):​c.425-1838T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0978 in 152,244 control chromosomes in the GnomAD database, including 918 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 0.098 (918 hom., cov: 32)
• Consequence: TNFSF13B ENST00000375887.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910

Genes affected

TNFSF13B (HGNC:11929): (TNF superfamily member 13b) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for receptors TNFRSF13B/TACI, TNFRSF17/BCMA, and TNFRSF13C/BAFFR. This cytokine is expressed in B cell lineage cells, and acts as a potent B cell activator. It has been also shown to play an important role in the proliferation and differentiation of B cells. Alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF13B	NM_006573.5	c.425-1838T>C		intron_variant		ENST00000375887.9	NP_006564.1
TNFSF13B	NM_001145645.2	c.424+14541T>C		intron_variant			NP_001139117.1
TNFSF13B	XM_047430055.1	c.425-1838T>C		intron_variant			XP_047286011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF13B	ENST00000375887.9	c.425-1838T>C		intron_variant		1	NM_006573.5	ENSP00000365048	P1
TNFSF13B	ENST00000430559.5	c.424+14541T>C		intron_variant		1		ENSP00000389540
TNFSF13B	ENST00000542136.1	c.425-1838T>C		intron_variant		1		ENSP00000445334
TNFSF13B	ENST00000479435.1	n.199-1838T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0979 AC: 14895 AN: 152124 Hom.: 919 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.129

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0978 AC: 14882 AN: 152244 Hom.: 918 Cov.: 32 AF XY: 0.0953 AC XY: 7096 AN XY: 74428

Gnomad4 AFR AF: 0.0362

Gnomad4 AMR AF: 0.0748

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0768

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.104

Alfa AF: 0.131 Hom.: 253

Bravo AF: 0.0896

Asia WGS AF: 0.0360 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.70

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: rs17499386; hg19: chr13-108937313;