chr13-108303821-T-A

Variant names:

• chr13-108303821-T-A
• rs1224146
• NM_006573.5:c.745+217T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006573.5(TNFSF13B):​c.745+217T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 152,126 control chromosomes in the GnomAD database, including 45,866 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.77 (45866 hom., cov: 33)
• Consequence: TNFSF13B NM_006573.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.265
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-108303821-T-A is Benign according to our data. Variant chr13-108303821-T-A is described in ClinVar as Benign. ClinVar VariationId is 1237091.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006573.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF13B	NM_006573.5	MANE Select	c.745+217T>A		intron	N/A	NP_006564.1	Q9Y275-1
	TNFSF13B	NM_001145645.2		c.688+217T>A		intron	N/A	NP_001139117.1	Q9Y275-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF13B	ENST00000375887.9	TSL:1 MANE Select	c.745+217T>A		intron	N/A	ENSP00000365048.3	Q9Y275-1
	TNFSF13B	ENST00000430559.5	TSL:1	c.688+217T>A		intron	N/A	ENSP00000389540.1	Q9Y275-2
	TNFSF13B	ENST00000493765.1	TSL:2	n.299+217T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117583 AN: 152008 Hom.: 45809 Cov.: 33

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.774 AC: 117694 AN: 152126 Hom.: 45866 Cov.: 33 AF XY: 0.769 AC XY: 57201 AN XY: 74370

African (AFR) AF: 0.841 AC: 34920 AN: 41520

American (AMR) AF: 0.821 AC: 12534 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2532 AN: 3472

East Asian (EAS) AF: 0.921 AC: 4771 AN: 5178

South Asian (SAS) AF: 0.685 AC: 3306 AN: 4824

European-Finnish (FIN) AF: 0.643 AC: 6788 AN: 10564

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50497 AN: 67976

Other (OTH) AF: 0.775 AC: 1639 AN: 2114

Alfa AF: 0.763 Hom.: 5221

Bravo AF: 0.790

Asia WGS AF: 0.789 AC: 2739 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.69
DANN	Benign	0.28
PhyloP100		0.27
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: rs1224146; hg19: chr13-108956169;