9-114796423-C-T

Position:

• chr9-114796423-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000374045.5(TNFSF15):​c.211-2855G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,200 control chromosomes in the GnomAD database, including 41,088 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 0.73 (41088 hom., cov: 33)
• Consequence: TNFSF15 ENST00000374045.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF15	NM_005118.4	c.211-2855G>A		intron_variant		ENST00000374045.5	NP_005109.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF15	ENST00000374045.5	c.211-2855G>A		intron_variant		1	NM_005118.4	ENSP00000363157	P1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110617 AN: 152080 Hom.: 41034 Cov.: 33

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.709

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.728 AC: 110734 AN: 152200 Hom.: 41088 Cov.: 33 AF XY: 0.728 AC XY: 54153 AN XY: 74384

Gnomad4 AFR AF: 0.867

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.729

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.711

Alfa AF: 0.674 Hom.: 76726

Bravo AF: 0.733

Asia WGS AF: 0.662 AC: 2300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.1
DANN	Benign	0.36

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: rs6478108; hg19: chr9-117558703;