rs12428930

chr13-108287357-A-Cchr13-108287357-A-G

Variant summary

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

The NM_006573.5(TNFSF13B):c.481+498A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,154 control chromosomes in the GnomAD database, including 4,107 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 0.21 (4107 hom., cov: 32)
• Consequence: TNFSF13B NM_006573.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.907

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF13B	NM_006573.5	c.481+498A>C		intron_variant		ENST00000375887.9
TNFSF13B	NM_001145645.2	c.425-15896A>C		intron_variant
TNFSF13B	XM_047430055.1	c.481+498A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF13B	ENST00000375887.9	c.481+498A>C		intron_variant		1	NM_006573.5	P1
TNFSF13B	ENST00000430559.5	c.425-15896A>C		intron_variant		1
TNFSF13B	ENST00000542136.1	c.481+498A>C		intron_variant		1
TNFSF13B	ENST00000479435.1	n.255+498A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31895 AN: 152038 Hom.: 4093 Cov.: 32

Gnomad AFR AF: 0.0871

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.210 AC: 31912 AN: 152154 Hom.: 4107 Cov.: 32 AF XY: 0.211 AC XY: 15701 AN XY: 74392

Gnomad4 AFR AF: 0.0869

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.243

Alfa AF: 0.206 Hom.: 1704

Bravo AF: 0.219

Asia WGS AF: 0.308 AC: 1072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.077
Dann	Benign	0.47

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: rs12428930; hg19: chr13-108939705;