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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF13B	NM_006573.5 link	c.746-85_746-84dupTT		intron_variant	Intron 5 of 5	ENST00000375887.9	NP_006564.1	Q9Y275-1A0A0U5J7Q1
TNFSF13B	NM_001145645.2 link	c.689-85_689-84dupTT		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.746-94_746-93insTT	intron_variant	Intron 5 of 5	1	NM_006573.5	ENSP00000365048.3	Q9Y275-1
TNFSF13B	ENST00000430559.5 link	c.689-94_689-93insTT	intron_variant	Intron 4 of 4	1		ENSP00000389540.1	Q9Y275-2
TNFSF13B	ENST00000493765.1 link	n.300-94_300-93insTT	intron_variant	Intron 1 of 1	2

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 v4.3

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over