Variant 17-43528665-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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 (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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 id is 2647814.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETV4	NM_001079675.5 link	c.1309C>T	p.Arg437Cys	missense_variant	13/13	ENST00000319349.10	NP_001073143.1	P43268-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETV4	ENST00000319349.10 link	c.1309C>T	p.Arg437Cys	missense_variant	13/13	1	NM_001079675.5	ENSP00000321835.4		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

GnomAD3 exomes

AF:

0.00761

AC:

1913

AN:

251416

Hom.:

AF XY:

0.00749

AC XY:

1018

AN XY:

135902

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 SAS exome

AF:

0.00108

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

Gnomad4 AFR exome

AF:

0.00176

Gnomad4 AMR exome

AF:

0.00440

Gnomad4 ASJ exome

AF:

0.00207

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00125

Gnomad4 FIN exome

AF:

0.00517

Gnomad4 NFE exome

AF:

0.0145

Gnomad4 OTH exome

AF:

0.0118

GnomAD4 genome

AF:

0.00773

AC:

1178

AN:

152298

Hom.:

Cov.:

AF XY:

0.00743

AC XY:

553

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.00654

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00395

Gnomad4 NFE

AF:

0.0128

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.0121

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

ETV4: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.81

.;D;D;.;T;D;.

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

D;.;.;.;D;D;D

MetaRNN

Benign

0.0085

T;T;T;T;T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.4

.;M;M;.;.;M;.

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-6.8

D;D;D;D;D;.;.

REVEL

Uncertain

0.30

Sift

Uncertain

0.022

D;D;D;D;D;.;.

Sift4G

Uncertain

0.046

D;D;D;D;D;D;D

Polyphen

1.0, 0.98

.;D;D;.;D;D;.

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

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