chr13-108284965-T-C

Variant names:

• chr13-108284965-T-C
• rs17499386
• NM_006573.5:c.425-1838T>C

Variant summary

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

The NM_006573.5(TNFSF13B):​c.425-1838T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0978 in 152,244 control chromosomes in the GnomAD database, including 918 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 0.098 (918 hom., cov: 32)
• Consequence: TNFSF13B NM_006573.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF13B	NM_006573.5	c.425-1838T>C		intron_variant	Intron 2 of 5	ENST00000375887.9	NP_006564.1
TNFSF13B	NM_001145645.2	c.424+14541T>C		intron_variant	Intron 2 of 4		NP_001139117.1
TNFSF13B	XM_047430055.1	c.425-1838T>C		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.425-1838T>C		intron_variant	Intron 2 of 5	1	NM_006573.5	ENSP00000365048.3
TNFSF13B	ENST00000430559.5	c.424+14541T>C		intron_variant	Intron 2 of 4	1		ENSP00000389540.1
TNFSF13B	ENST00000542136.1	c.425-1838T>C		intron_variant	Intron 2 of 3	1		ENSP00000445334.1
TNFSF13B	ENST00000479435.1	n.199-1838T>C		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.0979 AC: 14895 AN: 152124 Hom.: 919 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.129

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0978 AC: 14882 AN: 152244 Hom.: 918 Cov.: 32 AF XY: 0.0953 AC XY: 7096 AN XY: 74428

African (AFR) AF: 0.0362 AC: 1506 AN: 41558

American (AMR) AF: 0.0748 AC: 1144 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 529 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0768 AC: 371 AN: 4828

European-Finnish (FIN) AF: 0.114 AC: 1210 AN: 10588

Middle Eastern (MID) AF: 0.128 AC: 37 AN: 290

European-Non Finnish (NFE) AF: 0.145 AC: 9838 AN: 68008

Other (OTH) AF: 0.104 AC: 219 AN: 2114

Alfa AF: 0.121 Hom.: 634

Bravo AF: 0.0896

Asia WGS AF: 0.0360 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.70
PhyloP100		-0.091
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: rs17499386; hg19: chr13-108937313;