9-114790878-A-T

Position:

chr9-114790878-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005118.4(TNFSF15):c.330T>A(p.Phe110Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,614,128 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0076 ( 9 hom., cov: 31)

Exomes 𝑓: 0.0021 ( 38 hom. )

Consequence

TNFSF15
NM_005118.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.166

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020623207).

BP6

Variant 9-114790878-A-T is Benign according to our data. Variant chr9-114790878-A-T is described in ClinVar as [Benign]. Clinvar id is 768323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00757 (1152/152258) while in subpopulation EAS AF= 0.033 (171/5184). AF 95% confidence interval is 0.0289. There are 9 homozygotes in gnomad4. There are 589 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF15	NM_005118.4 linkuse as main transcript	c.330T>A	p.Phe110Leu	missense_variant	4/4	ENST00000374045.5
TNFSF15	NM_001204344.1 linkuse as main transcript	c.153T>A	p.Phe51Leu	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF15	ENST00000374045.5 linkuse as main transcript	c.330T>A	p.Phe110Leu	missense_variant	4/4	1	NM_005118.4	P1	O95150-1
TNFSF15	ENST00000374044.1 linkuse as main transcript	c.99T>A	p.Phe33Leu	missense_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.00757

AC:

1152

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0204

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0331

Gnomad SAS

AF:

0.00912

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00566

AC:

1413

AN:

249534

Hom.:

AF XY:

0.00547

AC XY:

738

AN XY:

135004

show subpopulations

Gnomad AFR exome

AF:

0.0189

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.0351

Gnomad SAS exome

AF:

0.00980

Gnomad FIN exome

AF:

0.00245

Gnomad NFE exome

AF:

0.000429

Gnomad OTH exome

AF:

0.00344

GnomAD4 exome

AF:

0.00206

AC:

3006

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

1569

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0203

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0233

Gnomad4 SAS exome

AF:

0.00868

Gnomad4 FIN exome

AF:

0.00258

Gnomad4 NFE exome

AF:

0.000166

Gnomad4 OTH exome

AF:

0.00432

GnomAD4 genome

AF:

0.00757

AC:

1152

AN:

152258

Hom.:

Cov.:

AF XY:

0.00791

AC XY:

589

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0203

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0330

Gnomad4 SAS

AF:

0.00913

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00185

Hom.:

Bravo

AF:

0.00799

ESP6500AA

AF:

0.0200

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00609

AC:

739

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.0

DANN

Benign

0.72

DEOGEN2

Benign

0.049

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.087

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.3

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.73

N;N

REVEL

Benign

0.050

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.034

MutPred

0.13

Loss of methylation at K111 (P = 0.033);.;

MVP

0.38

MPC

0.13

ClinPred

0.0029

GERP RS

3.0

Varity_R

0.21

gMVP

0.22

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over