Genetic Variant TNFSF13B:c.746-85_746-84delTT (chr13-108306732-ATT-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006573.5(TNFSF13B):c.746-85_746-84delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000458 in 437,058 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000046 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TNFSF13B
NM_006573.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.431

Publications

0 publications found

Variant links:

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]

TNFSF13B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.746-85_746-84delTT		intron	N/A	NP_006564.1	Q9Y275-1
	TNFSF13B	NM_001145645.2		c.689-85_689-84delTT		intron	N/A	NP_001139117.1	Q9Y275-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNFSF13B	ENST00000375887.9	TSL:1 MANE Select	c.746-93_746-92delTT	intron	N/A	ENSP00000365048.3	Q9Y275-1
TNFSF13B	ENST00000430559.5	TSL:1	c.689-93_689-92delTT	intron	N/A	ENSP00000389540.1	Q9Y275-2
TNFSF13B	ENST00000493765.1	TSL:2	n.300-93_300-92delTT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149334

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000458

AC:

AN:

437058

Hom.:

AF XY:

0.00

AC XY:

AN XY:

230966

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

9218

American (AMR)

AF:

0.00

AC:

AN:

13334

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12278

East Asian (EAS)

AF:

0.00

AC:

AN:

21524

South Asian (SAS)

AF:

0.00

AC:

AN:

37750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2636

European-Non Finnish (NFE)

AF:

0.00000349

AC:

AN:

286302

Other (OTH)

AF:

0.0000438

AC:

AN:

22810

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

149334

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72792

African (AFR)

AF:

0.00

AC:

AN:

40824

American (AMR)

AF:

0.00

AC:

AN:

14928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9824

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67160

Other (OTH)

AF:

0.00

AC:

AN:

2030

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.43

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

13-108306732-ATTT-AT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over