chr13-108270295-C-G

Variant names:

• chr13-108270295-C-G
• rs56124946
• NM_006573.5:c.340-45C>G

Variant summary

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

The NM_006573.5(TNFSF13B):​c.340-45C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 1,613,232 control chromosomes in the GnomAD database, including 2,462 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 0.031 (269 hom., cov: 32)
  • Exomes 𝑓: 0.021 (2193 hom.)
• Consequence: TNFSF13B NM_006573.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF13B	NM_006573.5	c.340-45C>G		intron_variant	Intron 1 of 5	ENST00000375887.9	NP_006564.1
TNFSF13B	NM_001145645.2	c.340-45C>G		intron_variant	Intron 1 of 4		NP_001139117.1
TNFSF13B	XM_047430055.1	c.340-45C>G		intron_variant	Intron 1 of 4		XP_047286011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF13B	ENST00000375887.9	c.340-45C>G		intron_variant	Intron 1 of 5	1	NM_006573.5	ENSP00000365048.3

Frequencies

GnomAD3 genomes AF: 0.0314 AC: 4771 AN: 152180 Hom.: 268 Cov.: 32

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0246

Gnomad FIN AF: 0.00349

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00774

Gnomad OTH AF: 0.0325

GnomAD2 exomes AF: 0.0566 AC: 14199 AN: 251012 AF XY: 0.0466

Gnomad AFR exome AF: 0.0254

Gnomad AMR exome AF: 0.266

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.148

Gnomad FIN exome AF: 0.00283

Gnomad NFE exome AF: 0.00806

Gnomad OTH exome AF: 0.0379

GnomAD4 exome AF: 0.0215 AC: 31390 AN: 1460932 Hom.: 2193 Cov.: 31 AF XY: 0.0202 AC XY: 14685 AN XY: 726862

African (AFR) AF: 0.0247 AC: 827 AN: 33456

American (AMR) AF: 0.251 AC: 11221 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00122 AC: 32 AN: 26126

East Asian (EAS) AF: 0.150 AC: 5965 AN: 39694

South Asian (SAS) AF: 0.0214 AC: 1844 AN: 86238

European-Finnish (FIN) AF: 0.00315 AC: 168 AN: 53350

Middle Eastern (MID) AF: 0.00399 AC: 23 AN: 5762

European-Non Finnish (NFE) AF: 0.00899 AC: 9990 AN: 1111224

Other (OTH) AF: 0.0219 AC: 1320 AN: 60366

GnomAD4 genome AF: 0.0314 AC: 4776 AN: 152300 Hom.: 269 Cov.: 32 AF XY: 0.0333 AC XY: 2483 AN XY: 74474

African (AFR) AF: 0.0279 AC: 1158 AN: 41570

American (AMR) AF: 0.140 AC: 2139 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.140 AC: 723 AN: 5164

South Asian (SAS) AF: 0.0248 AC: 120 AN: 4830

European-Finnish (FIN) AF: 0.00349 AC: 37 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00775 AC: 527 AN: 68036

Other (OTH) AF: 0.0326 AC: 69 AN: 2114

Alfa AF: 0.0166 Hom.: 31

Bravo AF: 0.0462

Asia WGS AF: 0.0770 AC: 267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.42
PhyloP100		-0.66
PromoterAI		-0.0084	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56124946; hg19: chr13-108922643;