Variant chr17-43528880-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001079675.5(ETV4):c.1231-137A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 725,604 control chromosomes in the GnomAD database, including 24,094 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.23 ( 4141 hom., cov: 31)

Exomes 𝑓: 0.26 ( 19953 hom. )

Consequence

ETV4
NM_001079675.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.112

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 17-43528880-T-C is Benign according to our data. Variant chr17-43528880-T-C is described in ClinVar as [Benign]. Clinvar id is 1243936.Status of the report is criteria_provided_single_submitter, 1 stars.

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/exons	MANE	Protein	UniProt
ETV4	NM_001079675.5 linkuse as main transcript	c.1231-137A>G		intron_variant		ENST00000319349.10	NP_001073143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETV4	ENST00000319349.10 linkuse as main transcript	c.1231-137A>G		intron_variant		1	NM_001079675.5	ENSP00000321835	P1	P43268-1

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34380

AN:

151956

Hom.:

4141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.244

GnomAD4 exome

AF:

0.259

AC:

148507

AN:

573530

Hom.:

19953

AF XY:

0.260

AC XY:

77592

AN XY:

297886

show subpopulations

Gnomad4 AFR exome

AF:

0.149

Gnomad4 AMR exome

AF:

0.215

Gnomad4 ASJ exome

AF:

0.298

Gnomad4 EAS exome

AF:

0.370

Gnomad4 SAS exome

AF:

0.265

Gnomad4 FIN exome

AF:

0.277

Gnomad4 NFE exome

AF:

0.253

Gnomad4 OTH exome

AF:

0.243

GnomAD4 genome

AF:

0.226

AC:

34381

AN:

152074

Hom.:

4141

Cov.:

AF XY:

0.229

AC XY:

16996

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.146

Gnomad4 AMR

AF:

0.211

Gnomad4 ASJ

AF:

0.308

Gnomad4 EAS

AF:

0.323

Gnomad4 SAS

AF:

0.267

Gnomad4 FIN

AF:

0.281

Gnomad4 NFE

AF:

0.254

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.133

Hom.:

229

Bravo

AF:

0.218

Asia WGS

AF:

0.222

AC:

772

AN:

3478

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

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

7.8

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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