chr9-114790878-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

5 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

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.330T>A	p.Phe110Leu	missense	Exon 4 of 4	NP_005109.2
	TNFSF15	NM_001204344.1		c.153T>A	p.Phe51Leu	missense	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.330T>A	p.Phe110Leu	missense	Exon 4 of 4	ENSP00000363157.3	O95150-1
	TNFSF15	ENST00000374044.1	TSL:6	c.99T>A	p.Phe33Leu	missense	Exon 1 of 1	ENSP00000363156.1	X6R8I9

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

GnomAD2 exomes

AF:

0.00566

AC:

1413

AN:

249534

AF XY:

0.00547

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 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

African (AFR)

AF:

0.0203

AC:

681

AN:

33480

American (AMR)

AF:

0.00127

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.0233

AC:

926

AN:

39698

South Asian (SAS)

AF:

0.00868

AC:

749

AN:

86256

European-Finnish (FIN)

AF:

0.00258

AC:

138

AN:

53408

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000166

AC:

185

AN:

1112008

Other (OTH)

AF:

0.00432

AC:

261

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

177

354

531

708

885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00757

AC:

1152

AN:

152258

Hom.:

Cov.:

AF XY:

0.00791

AC XY:

589

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0203

AC:

845

AN:

41532

American (AMR)

AF:

0.00235

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.0330

AC:

171

AN:

5184

South Asian (SAS)

AF:

0.00913

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00217

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68020

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

120

179

239

299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.0

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.049

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.087

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.3

PhyloP100

0.17

PrimateAI

Benign

0.30

PROVEAN

Benign

0.73

REVEL

Benign

0.050

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

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

Mutation Taster

=97/3

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over