rs79158595

Positions:

• chr17-43545844-G-A
• chr17-43545844-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001079675.5(ETV4):​c.-51-176C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 598,508 control chromosomes in the GnomAD database, including 27,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5555 hom., cov: 32)
  • Exomes 𝑓: 0.31 (21611 hom.)
• Consequence: ETV4 NM_001079675.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.360

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]

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 17-43545844-G-A is Benign according to our data. Variant chr17-43545844-G-A is described in ClinVar as [Benign]. Clinvar id is 1256771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETV4	NM_001079675.5	c.-51-176C>T		intron_variant		ENST00000319349.10	NP_001073143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETV4	ENST00000319349.10	c.-51-176C>T		intron_variant		1	NM_001079675.5	ENSP00000321835	P1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38416 AN: 151854 Hom.: 5555 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.306 AC: 136844 AN: 446534 Hom.: 21611 Cov.: 3 AF XY: 0.307 AC XY: 72485 AN XY: 236436

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.371

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.378

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.253 AC: 38417 AN: 151974 Hom.: 5555 Cov.: 32 AF XY: 0.256 AC XY: 19027 AN XY: 74262

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.250

Alfa AF: 0.258 Hom.: 782

Bravo AF: 0.234

Asia WGS AF: 0.218 AC: 758 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs79158595; hg19: chr17-41623212;