dbSNP rs61972017: TNFSF13B:c.746-61A>C (chr13-108306765-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_006573.5(TNFSF13B):c.746-61A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 995,560 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.012 ( 13 hom., cov: 28)

Exomes 𝑓: 0.015 ( 115 hom. )

Consequence

TNFSF13B
NM_006573.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.788

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0119 (1806/151490) while in subpopulation NFE AF = 0.0173 (1174/67776). AF 95% confidence interval is 0.0165. There are 13 homozygotes in GnomAd4. There are 867 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF13B	NM_006573.5 link	c.746-61A>C		intron_variant	Intron 5 of 5	ENST00000375887.9	NP_006564.1	Q9Y275-1A0A0U5J7Q1
TNFSF13B	NM_001145645.2 link	c.689-61A>C		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.746-61A>C	intron_variant	Intron 5 of 5	1	NM_006573.5	ENSP00000365048.3	Q9Y275-1
TNFSF13B	ENST00000430559.5 link	c.689-61A>C	intron_variant	Intron 4 of 4	1		ENSP00000389540.1	Q9Y275-2
TNFSF13B	ENST00000493765.1 link	n.300-61A>C	intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1807

AN:

151374

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00361

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.0338

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0131

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0173

Gnomad OTH

AF:

0.0140

GnomAD4 exome

AF:

0.0151

AC:

12724

AN:

844070

Hom.:

115

AF XY:

0.0148

AC XY:

6479

AN XY:

438358

show subpopulations

African (AFR)

AF:

0.00261

AC:

AN:

17998

American (AMR)

AF:

0.00814

AC:

241

AN:

29612

Ashkenazi Jewish (ASJ)

AF:

0.0309

AC:

624

AN:

20214

East Asian (EAS)

AF:

0.0000310

AC:

AN:

32290

South Asian (SAS)

AF:

0.00272

AC:

169

AN:

62028

European-Finnish (FIN)

AF:

0.0146

AC:

704

AN:

48342

Middle Eastern (MID)

AF:

0.00136

AC:

AN:

4420

European-Non Finnish (NFE)

AF:

0.0176

AC:

10391

AN:

590146

Other (OTH)

AF:

0.0139

AC:

541

AN:

39020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

586

1172

1759

2345

2931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

282

564

846

1128

1410

<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:

0.0119

AC:

1806

AN:

151490

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

867

AN XY:

74018

show subpopulations

African (AFR)

AF:

0.00360

AC:

149

AN:

41378

American (AMR)

AF:

0.0119

AC:

180

AN:

15186

Ashkenazi Jewish (ASJ)

AF:

0.0338

AC:

117

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5132

South Asian (SAS)

AF:

0.00228

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0131

AC:

137

AN:

10440

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0173

AC:

1174

AN:

67776

Other (OTH)

AF:

0.0139

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

188

282

376

470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0156

Hom.:

Bravo

AF:

0.0113

Asia WGS

AF:

0.000868

AC:

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.0

(source)

DANN

Benign

0.66

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism

(source)

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over