chr13-108303116-C-G

Position:

• chr13-108303116-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006573.5(TNFSF13B):​c.482-137C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 703,750 control chromosomes in the GnomAD database, including 210,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46949 hom., cov: 31)
  • Exomes 𝑓: 0.77 (163184 hom.)
• Consequence: TNFSF13B NM_006573.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.203

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 13-108303116-C-G is Benign according to our data. Variant chr13-108303116-C-G is described in ClinVar as [Benign]. Clinvar id is 1222988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF13B	NM_006573.5	c.482-137C>G		intron_variant		ENST00000375887.9
TNFSF13B	NM_001145645.2	c.425-137C>G		intron_variant
TNFSF13B	XM_047430055.1	c.*-137C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF13B	ENST00000375887.9	c.482-137C>G		intron_variant		1	NM_006573.5	P1
TNFSF13B	ENST00000430559.5	c.425-137C>G		intron_variant		1
TNFSF13B	ENST00000542136.1	c.482-338C>G		intron_variant		1
TNFSF13B	ENST00000479435.1	n.374-137C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119039 AN: 151850 Hom.: 46893 Cov.: 31

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.783

GnomAD4 exome AF: 0.767 AC: 423262 AN: 551782 Hom.: 163184 AF XY: 0.763 AC XY: 217566 AN XY: 285092

Gnomad4 AFR exome AF: 0.837

Gnomad4 AMR exome AF: 0.840

Gnomad4 ASJ exome AF: 0.720

Gnomad4 EAS exome AF: 0.886

Gnomad4 SAS exome AF: 0.689

Gnomad4 FIN exome AF: 0.694

Gnomad4 NFE exome AF: 0.768

Gnomad4 OTH exome AF: 0.767

GnomAD4 genome AF: 0.784 AC: 119149 AN: 151968 Hom.: 46949 Cov.: 31 AF XY: 0.779 AC XY: 57910 AN XY: 74292

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.923

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.765

Gnomad4 OTH AF: 0.784

Alfa AF: 0.716 Hom.: 2035

Bravo AF: 0.797

Asia WGS AF: 0.786 AC: 2725 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.41

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: rs1224145; hg19: chr13-108955464;