13-108283554-A-T

Variant names:

• chr13-108283554-A-T
• rs7993590
• NM_006573.5:c.425-3249A>T

Variant summary

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

The NM_006573.5(TNFSF13B):​c.425-3249A>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 4,260 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 (4260 hom., cov: 32)
• Consequence: TNFSF13B NM_006573.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490
• Publications: 3 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF13B	NM_006573.5	c.425-3249A>T		intron_variant	Intron 2 of 5	ENST00000375887.9	NP_006564.1
TNFSF13B	NM_001145645.2	c.424+13130A>T		intron_variant	Intron 2 of 4		NP_001139117.1
TNFSF13B	XM_047430055.1	c.425-3249A>T		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.425-3249A>T		intron_variant	Intron 2 of 5	1	NM_006573.5	ENSP00000365048.3
TNFSF13B	ENST00000430559.5	c.424+13130A>T		intron_variant	Intron 2 of 4	1		ENSP00000389540.1
TNFSF13B	ENST00000542136.1	c.425-3249A>T		intron_variant	Intron 2 of 3	1		ENSP00000445334.1
TNFSF13B	ENST00000479435.1	n.199-3249A>T		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32877 AN: 152050 Hom.: 4246 Cov.: 32

Gnomad AFR AF: 0.0998

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.216 AC: 32898 AN: 152168 Hom.: 4260 Cov.: 32 AF XY: 0.217 AC XY: 16147 AN XY: 74378

African (AFR) AF: 0.0996 AC: 4137 AN: 41536

American (AMR) AF: 0.359 AC: 5491 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1117 AN: 3470

East Asian (EAS) AF: 0.439 AC: 2261 AN: 5150

South Asian (SAS) AF: 0.258 AC: 1245 AN: 4828

European-Finnish (FIN) AF: 0.196 AC: 2072 AN: 10594

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.231 AC: 15710 AN: 67982

Other (OTH) AF: 0.253 AC: 535 AN: 2114

Alfa AF: 0.216 Hom.: 491

Bravo AF: 0.226

Asia WGS AF: 0.311 AC: 1081 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	2.0
DANN	Benign	0.37
PhyloP100		-0.049
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: rs7993590; hg19: chr13-108935902;