Genetic Variant NM_006573.5: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;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF13B	NM_006573.5 link	c.746-85_746-84delTT		intron_variant	Intron 5 of 5	ENST00000375887.9	NP_006564.1	Q9Y275-1A0A0U5J7Q1
TNFSF13B	NM_001145645.2 link	c.689-85_689-84delTT		intron_variant	Intron 4 of 4		NP_001139117.1	Q9Y275-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNFSF13B	ENST00000375887.9 link	c.746-93_746-92delTT	intron_variant	Intron 5 of 5	1	NM_006573.5	ENSP00000365048.3	Q9Y275-1
TNFSF13B	ENST00000430559.5 link	c.689-93_689-92delTT	intron_variant	Intron 4 of 4	1		ENSP00000389540.1	Q9Y275-2
TNFSF13B	ENST00000493765.1 link	n.300-93_300-92delTT	intron_variant	Intron 1 of 1	2

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 v4.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over