rs7853287

Positions:

• chr9-114787047-G-A

Variant summary

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

The NM_005118.4(TNFSF15):​c.*3405C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 151,942 control chromosomes in the GnomAD database, including 2,649 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 0.17 (2649 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNFSF15 NM_005118.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF15	NM_005118.4	c.*3405C>T		3_prime_UTR_variant	4/4	ENST00000374045.5	NP_005109.2
TNFSF15	NM_001204344.1	c.*3405C>T		3_prime_UTR_variant	2/2		NP_001191273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF15	ENST00000374045.5	c.*3405C>T		3_prime_UTR_variant	4/4	1	NM_005118.4	ENSP00000363157.3

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25904 AN: 151824 Hom.: 2652 Cov.: 32

Gnomad AFR AF: 0.0757

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.193

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.170 AC: 25903 AN: 151942 Hom.: 2649 Cov.: 32 AF XY: 0.167 AC XY: 12414 AN XY: 74264

Gnomad4 AFR AF: 0.0757

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.191

Alfa AF: 0.200 Hom.: 451

Bravo AF: 0.160

Asia WGS AF: 0.0740 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.4
DANN	Benign	0.63

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: rs7853287; hg19: chr9-117549327;