rs3810936

Positions:

• chr9-114790605-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530

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]

ACMG classification

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	c.603A>G	p.Val201Val	synonymous_variant	4/4	ENST00000374045.5	NP_005109.2
TNFSF15	NM_001204344.1	c.426A>G	p.Val142Val	synonymous_variant	2/2		NP_001191273.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113364 AN: 151774 Hom.: 43150 Cov.: 30

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

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.: 84 AF XY: 0.693 AC XY: 503903 AN XY: 727208

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.: 30 AF XY: 0.748 AC XY: 55519 AN XY: 74202

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

Other links and lift over

dbSNP: rs3810936; hg19: chr9-117552885; COSMIC: COSV65010024;