Genetic Variant TNFSF15:c.*4960A>G (chr9-114785492-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.75 ( 43317 hom., cov: 32)

Exomes 𝑓: 0.67 ( 2 hom. )

Consequence

TNFSF15
NM_005118.4 3_prime_UTR

Scores

Clinical Significance

Uncertain risk allele no assertion criteria provided O:1

Conservation

PhyloP100: -0.0110

Publications

22 publications found

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]

TNFSF15 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF15	NM_005118.4 link	c.*4960A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000374045.5	NP_005109.2	O95150-1A0A0U5JA19
TNFSF15	NM_001204344.1 link	c.*4960A>G		3_prime_UTR_variant	Exon 2 of 2		NP_001191273.1	O95150-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF15	ENST00000374045.5 link	c.*4960A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_005118.4	ENSP00000363157.3		O95150-1

Frequencies

GnomAD3 genomes

AF:

0.747

AC:

113630

AN:

152046

Hom.:

43263

Cov.:

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:

AN:

Hom.:

Cov.:

AF XY:

0.600

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.588

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.748

AC:

113746

AN:

152164

Hom.:

43317

Cov.:

AF XY:

0.749

AC XY:

55740

AN XY:

74400

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1389

2777

4166

5554

6943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.704

Hom.:

63235

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

Jun 10, 2022

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

Significance:Uncertain risk allele

Review Status:no assertion criteria provided

Collection Method:case-control

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.2

(source)

DANN

Benign

0.84

PhyloP100

-0.011

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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9-114785492-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over