rs16972217

Positions:

• chr13-108283099-C-T

Variant summary

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

The NM_006573.5(TNFSF13B):​c.425-3704C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,168 control chromosomes in the GnomAD database, including 4,229 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 0.22 (4229 hom., cov: 33)
• Consequence: TNFSF13B NM_006573.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF13B	NM_006573.5	c.425-3704C>T		intron_variant		ENST00000375887.9	NP_006564.1
TNFSF13B	NM_001145645.2	c.424+12675C>T		intron_variant			NP_001139117.1
TNFSF13B	XM_047430055.1	c.425-3704C>T		intron_variant			XP_047286011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF13B	ENST00000375887.9	c.425-3704C>T		intron_variant		1	NM_006573.5	ENSP00000365048	P1
TNFSF13B	ENST00000430559.5	c.424+12675C>T		intron_variant		1		ENSP00000389540
TNFSF13B	ENST00000542136.1	c.425-3704C>T		intron_variant		1		ENSP00000445334
TNFSF13B	ENST00000479435.1	n.199-3704C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32779 AN: 152050 Hom.: 4215 Cov.: 33

Gnomad AFR AF: 0.0994

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.216 AC: 32800 AN: 152168 Hom.: 4229 Cov.: 33 AF XY: 0.216 AC XY: 16097 AN XY: 74382

Gnomad4 AFR AF: 0.0992

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.252

Alfa AF: 0.241 Hom.: 7759

Bravo AF: 0.226

Asia WGS AF: 0.310 AC: 1079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.95
DANN	Benign	0.40

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: rs16972217; hg19: chr13-108935447;