chr9-114785492-T-C

Position:

• chr9-114785492-T-C

Variant summary

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

The NM_005118.4(TNFSF15):​c.*4960A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 152,176 control chromosomes in the GnomAD database, including 43,319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain risk allele (no stars).

• Frequency:
  • Genomes: 𝑓 0.75 (43317 hom., cov: 32)
  • Exomes 𝑓: 0.67 (2 hom.)
• Consequence: TNFSF15 NM_005118.4 3_prime_UTR
• Clinical Significance: Uncertain risk allele no assertion criteria provided O:1
• Conservation: PhyloP100: -0.0110

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF15	NM_005118.4	c.*4960A>G		3_prime_UTR_variant	4/4	ENST00000374045.5
TNFSF15	NM_001204344.1	c.*4960A>G		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF15	ENST00000374045.5	c.*4960A>G		3_prime_UTR_variant	4/4	1	NM_005118.4	P1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113630 AN: 152046 Hom.: 43263 Cov.: 32

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.716

GnomAD4 exome AF: 0.667 AC: 8 AN: 12 Hom.: 2 Cov.: 0 AF XY: 0.600 AC XY: 6 AN XY: 10

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.748 AC: 113746 AN: 152164 Hom.: 43317 Cov.: 32 AF XY: 0.749 AC XY: 55740 AN XY: 74400

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.782

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.716

Alfa AF: 0.697 Hom.: 48785

Bravo AF: 0.746

Asia WGS AF: 0.638 AC: 2218 AN: 3478

ClinVar

Significance: Uncertain risk allele

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Leprosy, susceptibility to, 1 Other:1

Uncertain risk allele, no assertion criteria provided

case-control

Centro Dermatológico Federico Lleras Acosta, Hospital Universitario Centro Dermatológico Federico Lleras Acosta

Jun 10, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.2
DANN	Benign	0.84

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: rs10114470; hg19: chr9-117547772;