9-114804733-C-T

Variant names:

• chr9-114804733-C-T
• rs4979462
• NM_005118.4:c.210+1070G>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.210+1070G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,138 control chromosomes in the GnomAD database, including 2,940 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 0.13 (2940 hom., cov: 32)
• Consequence: TNFSF15 NM_005118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• Publications: 52 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF15	NM_005118.4	c.210+1070G>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.210+1070G>A		intron_variant	Intron 1 of 3	1	NM_005118.4	ENSP00000363157.3

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19472 AN: 152018 Hom.: 2919 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.0519

Gnomad FIN AF: 0.0953

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00722

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.128 AC: 19543 AN: 152138 Hom.: 2940 Cov.: 32 AF XY: 0.132 AC XY: 9825 AN XY: 74418

African (AFR) AF: 0.331 AC: 13712 AN: 41444

American (AMR) AF: 0.154 AC: 2358 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3472

East Asian (EAS) AF: 0.275 AC: 1421 AN: 5164

South Asian (SAS) AF: 0.0511 AC: 247 AN: 4834

European-Finnish (FIN) AF: 0.0953 AC: 1011 AN: 10604

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00722 AC: 491 AN: 68014

Other (OTH) AF: 0.110 AC: 233 AN: 2112

Alfa AF: 0.0512 Hom.: 4105

Bravo AF: 0.147

Asia WGS AF: 0.160 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.82
PhyloP100		-0.27
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: rs4979462; hg19: chr9-117567013;