Genetic Variant ETV4:c.-169G>A (chr17-43546302-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001079675.5(ETV4):c.-169G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,120 control chromosomes in the GnomAD database, including 5,548 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5542 hom., cov: 31)

Exomes 𝑓: 0.24 ( 6 hom. )

Consequence

ETV4
NM_001079675.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.328

Publications

9 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETV4	NM_001079675.5 link	c.-169G>A		5_prime_UTR_variant	Exon 1 of 13	ENST00000319349.10	NP_001073143.1	P43268-1
ETV4	NM_001261437.3 link	c.-175G>A		5_prime_UTR_variant	Exon 1 of 12		NP_001248366.1	P43268-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETV4	ENST00000319349.10 link	c.-169G>A		5_prime_UTR_variant	Exon 1 of 13	1	NM_001079675.5	ENSP00000321835.4		P43268-1

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38376

AN:

151804

Hom.:

5542

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.297

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.253

GnomAD4 exome

AF:

0.245

AC:

AN:

196

Hom.:

Cov.:

AF XY:

0.284

AC XY:

AN XY:

134

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.300

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.260

AC:

AN:

154

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.253

AC:

38377

AN:

151924

Hom.:

5542

Cov.:

AF XY:

0.256

AC XY:

19009

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.111

AC:

4620

AN:

41488

American (AMR)

AF:

0.227

AC:

3478

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

1025

AN:

3472

East Asian (EAS)

AF:

0.317

AC:

1618

AN:

5112

South Asian (SAS)

AF:

0.275

AC:

1325

AN:

4810

European-Finnish (FIN)

AF:

0.391

AC:

4133

AN:

10564

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.314

AC:

21289

AN:

67876

Other (OTH)

AF:

0.250

AC:

526

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1383

2766

4148

5531

6914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.273

Hom.:

1011

Bravo

AF:

0.234

Asia WGS

AF:

0.220

AC:

764

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

0.33

PromoterAI

0.17

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=294/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.32

Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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17-43546302-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over