Genetic Variant TNFSF4:p.Ile62Ile (chr1-173188537-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003326.5(TNFSF4):c.186C>T(p.Ile62Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,612,050 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

TNFSF4
NM_003326.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0920

Publications

0 publications found

Variant links:

Genes affected

TNFSF4 (HGNC:11934): (TNF superfamily member 4) This gene encodes a cytokine of the tumor necrosis factor (TNF) ligand family. The encoded protein functions in T cell antigen-presenting cell (APC) interactions and mediates adhesion of activated T cells to endothelial cells. Polymorphisms in this gene have been associated with Sjogren's syndrome and systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

TNFSF4 Gene-Disease associations (from GenCC):

systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
myocardial infarction, susceptibility to
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

TNFSF4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-173188537-G-A is Benign according to our data. Variant chr1-173188537-G-A is described in ClinVar as Benign. ClinVar VariationId is 772822.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.092 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003326.5. 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
	TNFSF4	NM_003326.5	MANE Select	c.186C>T	p.Ile62Ile	synonymous	Exon 2 of 3	NP_003317.1	P23510-1
	TNFSF4	NM_001297562.2		c.36C>T	p.Ile12Ile	synonymous	Exon 2 of 3	NP_001284491.1	P23510-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNFSF4	ENST00000281834.4	TSL:1 MANE Select	c.186C>T	p.Ile62Ile	synonymous	Exon 2 of 3	ENSP00000281834.3	P23510-1
TNFSF4	ENST00000367718.5	TSL:1	c.36C>T	p.Ile12Ile	synonymous	Exon 2 of 3	ENSP00000356691.1	P23510-2
TNFSF4	ENST00000714430.1		c.186C>T	p.Ile62Ile	synonymous	Exon 6 of 7	ENSP00000519699.1	P23510-1

Frequencies

GnomAD3 genomes

AF:

0.00152

AC:

232

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00528

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.000463

AC:

116

AN:

250624

AF XY:

0.000303

show subpopulations

Gnomad AFR exome

AF:

0.00597

Gnomad AMR exome

AF:

0.000523

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000179

AC:

262

AN:

1459756

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

118

AN XY:

726250

show subpopulations

African (AFR)

AF:

0.00568

AC:

190

AN:

33428

American (AMR)

AF:

0.000560

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.0000349

AC:

AN:

86050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1110300

Other (OTH)

AF:

0.000580

AC:

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00153

AC:

233

AN:

152294

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00529

AC:

220

AN:

41562

American (AMR)

AF:

0.000327

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000814

Hom.:

Bravo

AF:

0.00172

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.7

(source)

DANN

Benign

0.78

PhyloP100

0.092

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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