rs7030574

Positions:

• chr9-114805769-C-A
• chr9-114805769-C-T

Variant summary

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

The NM_005118.4(TNFSF15):​c.210+34G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,599,906 control chromosomes in the GnomAD database, including 184,590 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 0.40 (13709 hom., cov: 32)
  • Exomes 𝑓: 0.48 (170881 hom.)
• Consequence: TNFSF15 NM_005118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF15	NM_005118.4	c.210+34G>T		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+34G>T		intron_variant		1	NM_005118.4	ENSP00000363157.3

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61384 AN: 151978 Hom.: 13709 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.0617

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.421

GnomAD3 exomes AF: 0.422 AC: 102816 AN: 243692 Hom.: 23893 AF XY: 0.435 AC XY: 57463 AN XY: 132048

Gnomad AFR exome AF: 0.258

Gnomad AMR exome AF: 0.303

Gnomad ASJ exome AF: 0.575

Gnomad EAS exome AF: 0.0638

Gnomad SAS exome AF: 0.456

Gnomad FIN exome AF: 0.489

Gnomad NFE exome AF: 0.505

Gnomad OTH exome AF: 0.456

GnomAD4 exome AF: 0.477 AC: 690500 AN: 1447810 Hom.: 170881 Cov.: 30 AF XY: 0.479 AC XY: 344290 AN XY: 719316

Gnomad4 AFR exome AF: 0.251

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.0474

Gnomad4 SAS exome AF: 0.459

Gnomad4 FIN exome AF: 0.489

Gnomad4 NFE exome AF: 0.505

Gnomad4 OTH exome AF: 0.465

GnomAD4 genome AF: 0.404 AC: 61394 AN: 152096 Hom.: 13709 Cov.: 32 AF XY: 0.400 AC XY: 29761 AN XY: 74358

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.0614

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.422

Alfa AF: 0.404 Hom.: 2163

Bravo AF: 0.385

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.46

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: rs7030574; hg19: chr9-117568049; COSMIC: COSV65011689;