Genetic Variant TNFSF13B:c.746-85_746-84dupTT (chr13-108306732-A-ATT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_006573.5(TNFSF13B):c.746-85_746-84dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 566,498 control chromosomes in the GnomAD database, including 102 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0086 ( 63 hom., cov: 0)

Exomes 𝑓: 0.049 ( 39 hom. )

Consequence

TNFSF13B
NM_006573.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.431

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 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.746-85_746-84dupTT		intron	N/A	NP_006564.1	Q9Y275-1
	TNFSF13B	NM_001145645.2		c.689-85_689-84dupTT		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.746-94_746-93insTT	intron	N/A	ENSP00000365048.3	Q9Y275-1
TNFSF13B	ENST00000430559.5	TSL:1	c.689-94_689-93insTT	intron	N/A	ENSP00000389540.1	Q9Y275-2
TNFSF13B	ENST00000493765.1	TSL:2	n.300-94_300-93insTT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00862

AC:

1287

AN:

149280

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00332

Gnomad AMR

AF:

0.00362

Gnomad ASJ

AF:

0.00348

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.0105

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00340

Gnomad OTH

AF:

0.00837

GnomAD4 exome

AF:

0.0485

AC:

20231

AN:

417116

Hom.:

AF XY:

0.0481

AC XY:

10599

AN XY:

220346

show subpopulations

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

African (AFR)

AF:

0.0531

AC:

462

AN:

8706

American (AMR)

AF:

0.0585

AC:

736

AN:

12588

Ashkenazi Jewish (ASJ)

AF:

0.0426

AC:

500

AN:

11736

East Asian (EAS)

AF:

0.161

AC:

3232

AN:

20064

South Asian (SAS)

AF:

0.0399

AC:

1441

AN:

36110

European-Finnish (FIN)

AF:

0.0385

AC:

1159

AN:

30138

Middle Eastern (MID)

AF:

0.0231

AC:

AN:

2516

European-Non Finnish (NFE)

AF:

0.0420

AC:

11499

AN:

273604

Other (OTH)

AF:

0.0528

AC:

1144

AN:

21654

⚠️ 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: 0.303

Heterozygous variant carriers

1886

3773

5659

7546

9432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

238

476

714

952

1190

<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

AF:

0.00861

AC:

1286

AN:

149382

Hom.:

Cov.:

AF XY:

0.00988

AC XY:

720

AN XY:

72878

show subpopulations

African (AFR)

AF:

0.00178

AC:

AN:

40920

American (AMR)

AF:

0.00361

AC:

AN:

14938

Ashkenazi Jewish (ASJ)

AF:

0.00348

AC:

AN:

3448

East Asian (EAS)

AF:

0.140

AC:

716

AN:

5124

South Asian (SAS)

AF:

0.0103

AC:

AN:

4756

European-Finnish (FIN)

AF:

0.0135

AC:

132

AN:

9814

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00340

AC:

228

AN:

67134

Other (OTH)

AF:

0.00927

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

113

170

226

283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00449

Hom.:

1843

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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13-108306732-ATTT-ATTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over