rs61972017

Positions:

• chr13-108306765-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006573.5(TNFSF13B):​c.746-61A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 995,560 control chromosomes in the GnomAD database, including 128 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 0.012 (13 hom., cov: 28)
  • Exomes 𝑓: 0.015 (115 hom.)
• Consequence: TNFSF13B NM_006573.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.788

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=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0119 (1806/151490) while in subpopulation NFE AF= 0.0173 (1174/67776). AF 95% confidence interval is 0.0165. There are 13 homozygotes in gnomad4. There are 867 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF13B	NM_006573.5	c.746-61A>C		intron_variant		ENST00000375887.9
TNFSF13B	NM_001145645.2	c.689-61A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF13B	ENST00000375887.9	c.746-61A>C		intron_variant		1	NM_006573.5	P1
TNFSF13B	ENST00000430559.5	c.689-61A>C		intron_variant		1
TNFSF13B	ENST00000493765.1	n.300-61A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1807 AN: 151374 Hom.: 13 Cov.: 28

Gnomad AFR AF: 0.00361

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.0338

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0131

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0173

Gnomad OTH AF: 0.0140

GnomAD4 exome AF: 0.0151 AC: 12724 AN: 844070 Hom.: 115 AF XY: 0.0148 AC XY: 6479 AN XY: 438358

Gnomad4 AFR exome AF: 0.00261

Gnomad4 AMR exome AF: 0.00814

Gnomad4 ASJ exome AF: 0.0309

Gnomad4 EAS exome AF: 0.0000310

Gnomad4 SAS exome AF: 0.00272

Gnomad4 FIN exome AF: 0.0146

Gnomad4 NFE exome AF: 0.0176

Gnomad4 OTH exome AF: 0.0139

GnomAD4 genome AF: 0.0119 AC: 1806 AN: 151490 Hom.: 13 Cov.: 28 AF XY: 0.0117 AC XY: 867 AN XY: 74018

Gnomad4 AFR AF: 0.00360

Gnomad4 AMR AF: 0.0119

Gnomad4 ASJ AF: 0.0338

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0131

Gnomad4 NFE AF: 0.0173

Gnomad4 OTH AF: 0.0139

Alfa AF: 0.0156 Hom.: 0

Bravo AF: 0.0113

Asia WGS AF: 0.000868 AC: 3 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.66

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: rs61972017; hg19: chr13-108959113;