rs9520836

Positions:

• chr13-108304715-A-G
• chr13-108304715-A-T

Variant summary

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

The NM_006573.5(TNFSF13B):​c.745+1111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,120 control chromosomes in the GnomAD database, including 4,132 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 0.20 (4132 hom., cov: 32)
• Consequence: TNFSF13B NM_006573.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF13B	NM_006573.5	c.745+1111A>G		intron_variant		ENST00000375887.9
TNFSF13B	NM_001145645.2	c.688+1111A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF13B	ENST00000375887.9	c.745+1111A>G		intron_variant		1	NM_006573.5	P1
TNFSF13B	ENST00000430559.5	c.688+1111A>G		intron_variant		1
TNFSF13B	ENST00000493765.1	n.299+1111A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30692 AN: 152002 Hom.: 4128 Cov.: 32

Gnomad AFR AF: 0.0483

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.202 AC: 30700 AN: 152120 Hom.: 4132 Cov.: 32 AF XY: 0.204 AC XY: 15154 AN XY: 74364

Gnomad4 AFR AF: 0.0481

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.231

Alfa AF: 0.161 Hom.: 399

Bravo AF: 0.205

Asia WGS AF: 0.360 AC: 1251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.52
DANN	Benign	0.36

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: rs9520836; hg19: chr13-108957063;