Variant chr9-114790605-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TNFSF15	NM_005118.4 linkuse as main transcript	c.603A>G	p.Val201Val	synonymous_variant	4/4	ENST00000374045.5	NP_005109.2	O95150-1A0A0U5JA19
TNFSF15	NM_001204344.1 linkuse as main transcript	c.426A>G	p.Val142Val	synonymous_variant	2/2		NP_001191273.1	O95150-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF15	ENST00000374045.5 linkuse as main transcript	c.603A>G	p.Val201Val	synonymous_variant	4/4	1	NM_005118.4	ENSP00000363157.3		O95150-1
TNFSF15	ENST00000374044.1 linkuse as main transcript	c.372A>G	p.Val124Val	synonymous_variant	1/1	6		ENSP00000363156.1		X6R8I9

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

GnomAD3 exomes

AF:

0.708

AC:

177770

AN:

251132

Hom.:

63837

AF XY:

0.702

AC XY:

95250

AN XY:

135742

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 SAS exome

AF:

0.687

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

Gnomad4 AFR exome

AF:

0.898

Gnomad4 AMR exome

AF:

0.746

Gnomad4 ASJ exome

AF:

0.726

Gnomad4 EAS exome

AF:

0.544

Gnomad4 SAS exome

AF:

0.691

Gnomad4 FIN exome

AF:

0.774

Gnomad4 NFE exome

AF:

0.685

Gnomad4 OTH exome

AF:

0.701

GnomAD4 genome

AF:

0.747

AC:

113479

AN:

151892

Hom.:

43204

Cov.:

AF XY:

0.748

AC XY:

55519

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.890

Gnomad4 AMR

AF:

0.721

Gnomad4 ASJ

AF:

0.722

Gnomad4 EAS

AF:

0.497

Gnomad4 SAS

AF:

0.687

Gnomad4 FIN

AF:

0.775

Gnomad4 NFE

AF:

0.688

Gnomad4 OTH

AF:

0.720

Alfa

AF:

0.693

Hom.:

78681

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

DANN

Benign

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over