9-114804160-A-G

Position:

• chr9-114804160-A-G

Variant summary

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

The NM_005118.4(TNFSF15):​c.210+1643T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,142 control chromosomes in the GnomAD database, including 42,871 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 0.74 (42871 hom., cov: 32)
• Consequence: TNFSF15 NM_005118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF15	NM_005118.4	c.210+1643T>C		intron_variant		ENST00000374045.5	NP_005109.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF15	ENST00000374045.5	c.210+1643T>C		intron_variant		1	NM_005118.4	ENSP00000363157.3

Frequencies

GnomAD3 genomes AF: 0.743 AC: 113005 AN: 152024 Hom.: 42817 Cov.: 32

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.744 AC: 113121 AN: 152142 Hom.: 42871 Cov.: 32 AF XY: 0.743 AC XY: 55283 AN XY: 74372

Gnomad4 AFR AF: 0.887

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.724

Alfa AF: 0.688 Hom.: 66967

Bravo AF: 0.749

Asia WGS AF: 0.668 AC: 2322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.49

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: rs4263839; hg19: chr9-117566440;