NM_005118.4:c.*4960A>G

Variant names:

• chr9-114785492-T-C
• rs10114470
• NM_005118.4:c.*4960A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF15	NM_005118.4	MANE Select	c.*4960A>G		3_prime_UTR	Exon 4 of 4	NP_005109.2
	TNFSF15	NM_001204344.1		c.*4960A>G		3_prime_UTR	Exon 2 of 2	NP_001191273.1	O95150-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF15	ENST00000374045.5	TSL:1 MANE Select	c.*4960A>G		3_prime_UTR	Exon 4 of 4	ENSP00000363157.3	O95150-1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 6 AN: 8

Other (OTH) AF: 0.500 AC: 2 AN: 4

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

African (AFR) AF: 0.890 AC: 36971 AN: 41536

American (AMR) AF: 0.721 AC: 11017 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2498 AN: 3472

East Asian (EAS) AF: 0.499 AC: 2580 AN: 5168

South Asian (SAS) AF: 0.697 AC: 3360 AN: 4824

European-Finnish (FIN) AF: 0.782 AC: 8286 AN: 10596

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46733 AN: 67974

Other (OTH) AF: 0.716 AC: 1510 AN: 2108

Alfa AF: 0.704 Hom.: 63235

Bravo AF: 0.746

Asia WGS AF: 0.638 AC: 2218 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain risk allele

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Leprosy, susceptibility to, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.2
DANN	Benign	0.84
PhyloP100		-0.011
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: rs10114470; hg19: chr9-117547772;