rs16972216

Variant names:

• chr13-108282272-G-A
• rs16972216
• NM_006573.5:c.425-4531G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006573.5(TNFSF13B):​c.425-4531G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,080 control chromosomes in the GnomAD database, including 2,843 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 0.17 (2843 hom., cov: 33)
• Consequence: TNFSF13B NM_006573.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF13B	NM_006573.5	c.425-4531G>A		intron_variant	Intron 2 of 5	ENST00000375887.9	NP_006564.1
TNFSF13B	NM_001145645.2	c.424+11848G>A		intron_variant	Intron 2 of 4		NP_001139117.1
TNFSF13B	XM_047430055.1	c.425-4531G>A		intron_variant	Intron 2 of 4		XP_047286011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF13B	ENST00000375887.9	c.425-4531G>A		intron_variant	Intron 2 of 5	1	NM_006573.5	ENSP00000365048.3
TNFSF13B	ENST00000430559.5	c.424+11848G>A		intron_variant	Intron 2 of 4	1		ENSP00000389540.1
TNFSF13B	ENST00000542136.1	c.425-4531G>A		intron_variant	Intron 2 of 3	1		ENSP00000445334.1
TNFSF13B	ENST00000479435.1	n.199-4531G>A		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25750 AN: 151962 Hom.: 2829 Cov.: 33

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.169 AC: 25772 AN: 152080 Hom.: 2843 Cov.: 33 AF XY: 0.173 AC XY: 12869 AN XY: 74350

African (AFR) AF: 0.0802 AC: 3330 AN: 41514

American (AMR) AF: 0.306 AC: 4670 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 861 AN: 3470

East Asian (EAS) AF: 0.419 AC: 2165 AN: 5166

South Asian (SAS) AF: 0.247 AC: 1190 AN: 4824

European-Finnish (FIN) AF: 0.171 AC: 1810 AN: 10566

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11083 AN: 67948

Other (OTH) AF: 0.195 AC: 411 AN: 2112

Alfa AF: 0.180 Hom.: 4128

Bravo AF: 0.179

Asia WGS AF: 0.300 AC: 1044 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	3.5
DANN	Benign	0.73
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16972216; hg19: chr13-108934620;