rs56124946

Positions:

• chr13-108270295-C-G

Variant summary

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

The NM_006573.5(TNFSF13B):​c.340-45C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 1,613,232 control chromosomes in the GnomAD database, including 2,462 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 0.031 (269 hom., cov: 32)
  • Exomes 𝑓: 0.021 (2193 hom.)
• Consequence: TNFSF13B NM_006573.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF13B	NM_006573.5	c.340-45C>G		intron_variant		ENST00000375887.9	NP_006564.1
TNFSF13B	NM_001145645.2	c.340-45C>G		intron_variant			NP_001139117.1
TNFSF13B	XM_047430055.1	c.340-45C>G		intron_variant			XP_047286011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF13B	ENST00000375887.9	c.340-45C>G		intron_variant		1	NM_006573.5	ENSP00000365048	P1

Frequencies

GnomAD3 genomes AF: 0.0314 AC: 4771 AN: 152180 Hom.: 268 Cov.: 32

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0246

Gnomad FIN AF: 0.00349

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00774

Gnomad OTH AF: 0.0325

GnomAD3 exomes AF: 0.0566 AC: 14199 AN: 251012 Hom.: 1606 AF XY: 0.0466 AC XY: 6320 AN XY: 135694

Gnomad AFR exome AF: 0.0254

Gnomad AMR exome AF: 0.266

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.148

Gnomad SAS exome AF: 0.0218

Gnomad FIN exome AF: 0.00283

Gnomad NFE exome AF: 0.00806

Gnomad OTH exome AF: 0.0379

GnomAD4 exome AF: 0.0215 AC: 31390 AN: 1460932 Hom.: 2193 Cov.: 31 AF XY: 0.0202 AC XY: 14685 AN XY: 726862

Gnomad4 AFR exome AF: 0.0247

Gnomad4 AMR exome AF: 0.251

Gnomad4 ASJ exome AF: 0.00122

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.0214

Gnomad4 FIN exome AF: 0.00315

Gnomad4 NFE exome AF: 0.00899

Gnomad4 OTH exome AF: 0.0219

GnomAD4 genome AF: 0.0314 AC: 4776 AN: 152300 Hom.: 269 Cov.: 32 AF XY: 0.0333 AC XY: 2483 AN XY: 74474

Gnomad4 AFR AF: 0.0279

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.0248

Gnomad4 FIN AF: 0.00349

Gnomad4 NFE AF: 0.00775

Gnomad4 OTH AF: 0.0326

Alfa AF: 0.0166 Hom.: 31

Bravo AF: 0.0462

Asia WGS AF: 0.0770 AC: 267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56124946; hg19: chr13-108922643;