17-43528665-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001079675.5(ETV4):c.1309C>T(p.Arg437Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0116 in 1,614,178 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 12 hom., cov: 32)

Exomes 𝑓: 0.012 ( 135 hom. )

Consequence

ETV4
NM_001079675.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.79

Publications

20 publications found

Variant links:

Genes affected

ETV4 (HGNC:3493): (ETS variant transcription factor 4) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of keratinocyte differentiation and positive regulation of transcription by RNA polymerase II. Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ETV4 links:

DHX8 (HGNC:2749): (DEAH-box helicase 8) This gene is a member of the DEAH box polypeptide family. The encoded protein contains the DEAH (Asp-Glu-Ala-His) motif which is characteristic of all DEAH box proteins, and is thought to function as an ATP-dependent RNA helicase that regulates the release of spliced mRNAs from spliceosomes prior to their export from the nucleus. This protein may be required for the replication of human immunodeficiency virus type 1 (HIV-1). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

DHX8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008488297).

BP6

Variant 17-43528665-G-A is Benign according to our data. Variant chr17-43528665-G-A is described in ClinVar as Benign. ClinVar VariationId is 2647814.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 12 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079675.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ETV4	NM_001079675.5	MANE Select	c.1309C>T	p.Arg437Cys	missense	Exon 13 of 13	NP_001073143.1	P43268-1
ETV4	NM_001369366.2		c.1309C>T	p.Arg437Cys	missense	Exon 13 of 13	NP_001356295.1	P43268-1
ETV4	NM_001986.4		c.1309C>T	p.Arg437Cys	missense	Exon 13 of 13	NP_001977.1	P43268-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ETV4	ENST00000319349.10	TSL:1 MANE Select	c.1309C>T	p.Arg437Cys	missense	Exon 13 of 13	ENSP00000321835.4	P43268-1
ETV4	ENST00000393664.6	TSL:1	c.1309C>T	p.Arg437Cys	missense	Exon 12 of 12	ENSP00000377273.1	P43268-1
ETV4	ENST00000591713.5	TSL:1	c.1309C>T	p.Arg437Cys	missense	Exon 13 of 13	ENSP00000465718.1	P43268-1

Frequencies

GnomAD3 genomes

AF:

0.00774

AC:

1178

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.00655

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00395

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0128

Gnomad OTH

AF:

0.00718

GnomAD2 exomes

AF:

0.00761

AC:

1913

AN:

251416

AF XY:

0.00749

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00451

Gnomad ASJ exome

AF:

0.00347

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00494

Gnomad NFE exome

AF:

0.0131

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.0120

AC:

17570

AN:

1461880

Hom.:

135

Cov.:

AF XY:

0.0116

AC XY:

8464

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00176

AC:

AN:

33480

American (AMR)

AF:

0.00440

AC:

197

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00207

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00125

AC:

108

AN:

86258

European-Finnish (FIN)

AF:

0.00517

AC:

276

AN:

53414

Middle Eastern (MID)

AF:

0.0149

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0145

AC:

16077

AN:

1112004

Other (OTH)

AF:

0.0118

AC:

713

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

941

1882

2824

3765

4706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

598

1196

1794

2392

2990

<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:

0.00773

AC:

1178

AN:

152298

Hom.:

Cov.:

AF XY:

0.00743

AC XY:

553

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00195

AC:

AN:

41578

American (AMR)

AF:

0.00654

AC:

100

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5162

South Asian (SAS)

AF:

0.00249

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00395

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0128

AC:

874

AN:

68022

Other (OTH)

AF:

0.00710

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

122

184

245

306

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:

0.0117

Hom.:

Bravo

AF:

0.00795

TwinsUK

AF:

0.0132

AC:

ALSPAC

AF:

0.0158

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0121

AC:

104

ExAC

AF:

0.00756

AC:

918

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0115

EpiControl

AF:

0.0126

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

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.81

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.0085

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.4

PhyloP100

4.8

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-6.8

REVEL

Uncertain

0.30

Sift

Uncertain

0.022

Sift4G

Uncertain

0.046

Polyphen

1.0

Vest4

0.47

MVP

0.87

MPC

1.2

ClinPred

0.068

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.53

gMVP

0.78

Mutation Taster

=72/28

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