9-114785492-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Uncertain risk allele no assertion criteria provided O:1

Conservation

PhyloP100: -0.0110
Variant links:
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]

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ACMG classification

Classification made for transcript

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
TNFSF15NM_005118.4 linkuse as main transcriptc.*4960A>G 3_prime_UTR_variant 4/4 ENST00000374045.5
TNFSF15NM_001204344.1 linkuse as main transcriptc.*4960A>G 3_prime_UTR_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TNFSF15ENST00000374045.5 linkuse as main transcriptc.*4960A>G 3_prime_UTR_variant 4/41 NM_005118.4 P1O95150-1

Frequencies

GnomAD3 genomes
AF:
0.747
AC:
113630
AN:
152046
Hom.:
43263
Cov.:
32
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

Leprosy, susceptibility to, 1 Other:1
Uncertain risk allele, no assertion criteria providedcase-controlCentro Dermatológico Federico Lleras Acosta, Hospital Universitario Centro Dermatológico Federico Lleras AcostaJun 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10114470; hg19: chr9-117547772; API