Variant rs2271959 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001079675.5(ETV4):c.61-5C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,577,064 control chromosomes in the GnomAD database, including 72,834 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5645 hom., cov: 31)

Exomes 𝑓: 0.30 ( 67189 hom. )

Consequence

ETV4
NM_001079675.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.9988

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.35

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 -16 ACMG points.

BP6

Variant 17-43545372-G-T is Benign according to our data. Variant chr17-43545372-G-T is described in ClinVar as [Benign]. Clinvar id is 1295936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 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.61-5C>A		splice_region_variant, splice_polypyrimidine_tract_variant, 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.61-5C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001079675.5	ENSP00000321835	P1	P43268-1

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39009

AN:

152010

Hom.:

5646

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.297

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.318

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.254

GnomAD3 exomes

AF:

0.299

AC:

58046

AN:

193856

Hom.:

8727

AF XY:

0.304

AC XY:

31921

AN XY:

104966

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.299

Gnomad EAS exome

AF:

0.312

Gnomad SAS exome

AF:

0.280

Gnomad FIN exome

AF:

0.396

Gnomad NFE exome

AF:

0.324

Gnomad OTH exome

AF:

0.290

GnomAD4 exome

AF:

0.304

AC:

433781

AN:

1424936

Hom.:

67189

Cov.:

AF XY:

0.305

AC XY:

214815

AN XY:

705110

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.241

Gnomad4 ASJ exome

AF:

0.293

Gnomad4 EAS exome

AF:

0.364

Gnomad4 SAS exome

AF:

0.278

Gnomad4 FIN exome

AF:

0.384

Gnomad4 NFE exome

AF:

0.310

Gnomad4 OTH exome

AF:

0.283

GnomAD4 genome

AF:

0.256

AC:

39008

AN:

152128

Hom.:

5645

Cov.:

AF XY:

0.260

AC XY:

19337

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.229

Gnomad4 ASJ

AF:

0.301

Gnomad4 EAS

AF:

0.318

Gnomad4 SAS

AF:

0.277

Gnomad4 FIN

AF:

0.392

Gnomad4 NFE

AF:

0.314

Gnomad4 OTH

AF:

0.250

Alfa

AF:

0.257

Hom.:

2107

Bravo

AF:

0.238

Asia WGS

AF:

0.224

AC:

779

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Uncertain

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.82

SpliceAI score (max)

0.88

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.88

Position offset: -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