9-114796423-C-T

Variant names:

• chr9-114796423-C-T
• rs6478108
• NM_005118.4:c.211-2855G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005118.4(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 NM_005118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442
• Publications: 110 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TNFSF15	NM_005118.4	c.211-2855G>A		intron_variant	Intron 1 of 3	ENST00000374045.5	NP_005109.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF15	ENST00000374045.5	c.211-2855G>A		intron_variant	Intron 1 of 3	1	NM_005118.4	ENSP00000363157.3

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

African (AFR) AF: 0.867 AC: 36027 AN: 41538

American (AMR) AF: 0.735 AC: 11240 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2528 AN: 3470

East Asian (EAS) AF: 0.504 AC: 2605 AN: 5170

South Asian (SAS) AF: 0.720 AC: 3469 AN: 4820

European-Finnish (FIN) AF: 0.706 AC: 7484 AN: 10596

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.665 AC: 45220 AN: 68004

Other (OTH) AF: 0.711 AC: 1501 AN: 2112

Alfa AF: 0.685 Hom.: 157268

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
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6478108; hg19: chr9-117558703;