rs10508198

chr13-108290440-G-Cchr13-108290440-G-T

Variant summary

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

The NM_006573.5(TNFSF13B):c.481+3581G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,026 control chromosomes in the GnomAD database, including 5,658 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 0.25 (5658 hom., cov: 32)
• Consequence: TNFSF13B NM_006573.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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 = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF13B	NM_006573.5	c.481+3581G>C		intron_variant		ENST00000375887.9
TNFSF13B	NM_001145645.2	c.425-12813G>C		intron_variant
TNFSF13B	XM_047430055.1	c.481+3581G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF13B	ENST00000375887.9	c.481+3581G>C		intron_variant		1	NM_006573.5	P1
TNFSF13B	ENST00000430559.5	c.425-12813G>C		intron_variant		1
TNFSF13B	ENST00000542136.1	c.481+3581G>C		intron_variant		1
TNFSF13B	ENST00000479435.1	n.255+3581G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38619 AN: 151908 Hom.: 5660 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0942

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.254 AC: 38615 AN: 152026 Hom.: 5658 Cov.: 32 AF XY: 0.258 AC XY: 19156 AN XY: 74330

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.0935

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.255

Alfa AF: 0.134 Hom.: 225

Bravo AF: 0.236

Asia WGS AF: 0.185 AC: 646 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	0.23
Dann	Benign	0.54

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: rs10508198; hg19: chr13-108942788;