9-114804160-A-G

Variant names:

• chr9-114804160-A-G
• rs4263839
• NM_005118.4:c.210+1643T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 103 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005118.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF15	NM_005118.4	MANE Select	c.210+1643T>C		intron	N/A	NP_005109.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF15	ENST00000374045.5	TSL:1 MANE Select	c.210+1643T>C		intron	N/A	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

African (AFR) AF: 0.887 AC: 36825 AN: 41530

American (AMR) AF: 0.743 AC: 11363 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2565 AN: 3472

East Asian (EAS) AF: 0.507 AC: 2614 AN: 5156

South Asian (SAS) AF: 0.735 AC: 3550 AN: 4828

European-Finnish (FIN) AF: 0.713 AC: 7540 AN: 10574

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46330 AN: 67982

Other (OTH) AF: 0.724 AC: 1529 AN: 2112

Alfa AF: 0.701 Hom.: 151475

Bravo AF: 0.749

Asia WGS AF: 0.668 AC: 2322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.49
PhyloP100		-1.9
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: rs4263839; hg19: chr9-117566440;