Genetic Variant TNFSF15:p.Val201Val (chr9-114790605-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005118.4(TNFSF15):c.603A>G(p.Val201Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 1,613,702 control chromosomes in the GnomAD database, including 396,595 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 0.75 ( 43204 hom., cov: 30)

Exomes 𝑓: 0.69 ( 353391 hom. )

Consequence

TNFSF15
NM_005118.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.530

Publications

100 publications found

Variant links:

Genes affected

TNFSF15 (HGNC:11931): (TNF superfamily member 15) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is abundantly expressed in endothelial cells, but is not expressed in either B or T cells. The expression of this protein is inducible by TNF and IL-1 alpha. This cytokine is a ligand for receptor TNFRSF25 and decoy receptor TNFRSF21/DR6. It can activate NF-kappaB and MAP kinases, and acts as an autocrine factor to induce apoptosis in endothelial cells. This cytokine is also found to inhibit endothelial cell proliferation, and thus may function as an angiogenesis inhibitor. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

TNFSF15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP7

Synonymous conserved (PhyloP=0.53 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF15	NM_005118.4 link	c.603A>G	p.Val201Val	synonymous_variant	Exon 4 of 4	ENST00000374045.5	NP_005109.2
TNFSF15	NM_001204344.1 link	c.426A>G	p.Val142Val	synonymous_variant	Exon 2 of 2		NP_001191273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF15	ENST00000374045.5 link	c.603A>G	p.Val201Val	synonymous_variant	Exon 4 of 4	1	NM_005118.4	ENSP00000363157.3
TNFSF15	ENST00000374044.1 link	c.372A>G	p.Val124Val	synonymous_variant	Exon 1 of 1	6		ENSP00000363156.1

Frequencies

GnomAD3 genomes

AF:

0.747

AC:

113364

AN:

151774

Hom.:

43150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.890

Gnomad AMI

AF:

0.637

Gnomad AMR

AF:

0.721

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.497

Gnomad SAS

AF:

0.687

Gnomad FIN

AF:

0.775

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.688

Gnomad OTH

AF:

0.720

GnomAD2 exomes

AF:

0.708

AC:

177770

AN:

251132

AF XY:

0.702

show subpopulations

Gnomad AFR exome

AF:

0.893

Gnomad AMR exome

AF:

0.755

Gnomad ASJ exome

AF:

0.726

Gnomad EAS exome

AF:

0.470

Gnomad FIN exome

AF:

0.782

Gnomad NFE exome

AF:

0.696

Gnomad OTH exome

AF:

0.698

GnomAD4 exome

AF:

0.694

AC:

1013846

AN:

1461810

Hom.:

353391

Cov.:

AF XY:

0.693

AC XY:

503903

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.898

AC:

30073

AN:

33480

American (AMR)

AF:

0.746

AC:

33336

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.726

AC:

18963

AN:

26136

East Asian (EAS)

AF:

0.544

AC:

21571

AN:

39688

South Asian (SAS)

AF:

0.691

AC:

59638

AN:

86258

European-Finnish (FIN)

AF:

0.774

AC:

41354

AN:

53408

Middle Eastern (MID)

AF:

0.747

AC:

4309

AN:

5768

European-Non Finnish (NFE)

AF:

0.685

AC:

762236

AN:

1111964

Other (OTH)

AF:

0.701

AC:

42366

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

20471

40942

61412

81883

102354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19506

39012

58518

78024

97530

<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:

0.747

AC:

113479

AN:

151892

Hom.:

43204

Cov.:

AF XY:

0.748

AC XY:

55519

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.890

AC:

36904

AN:

41450

American (AMR)

AF:

0.721

AC:

10987

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.722

AC:

2505

AN:

3470

East Asian (EAS)

AF:

0.497

AC:

2549

AN:

5124

South Asian (SAS)

AF:

0.687

AC:

3304

AN:

4806

European-Finnish (FIN)

AF:

0.775

AC:

8157

AN:

10522

Middle Eastern (MID)

AF:

0.721

AC:

212

AN:

294

European-Non Finnish (NFE)

AF:

0.688

AC:

46761

AN:

67956

Other (OTH)

AF:

0.720

AC:

1519

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1396

2792

4187

5583

6979

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<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:

0.704

Hom.:

161857

Bravo

AF:

0.747

Asia WGS

AF:

0.638

AC:

2217

AN:

3478

EpiCase

AF:

0.684

EpiControl

AF:

0.688

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.3

(source)

DANN

Benign

0.63

PhyloP100

0.53

Mutation Taster

=98/2

polymorphism (auto)

(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

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

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