17-43529343-G-A

Position:

• chr17-43529343-G-A

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.1129-107C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,397,198 control chromosomes in the GnomAD database, including 11,175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1304 hom., cov: 31)
  • Exomes 𝑓: 0.12 (9871 hom.)
• Consequence: ETV4 NM_001079675.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.03

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=-0.72).
• BP6: Variant 17-43529343-G-A is Benign according to our data. Variant chr17-43529343-G-A is described in ClinVar as [Benign]. Clinvar id is 1266831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETV4	NM_001079675.5	c.1129-107C>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.1129-107C>T		intron_variant		1	NM_001079675.5	ENSP00000321835	P1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19139 AN: 151950 Hom.: 1305 Cov.: 31

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0830

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.0859

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.122 AC: 151669 AN: 1245130 Hom.: 9871 Cov.: 17 AF XY: 0.120 AC XY: 75495 AN XY: 626602

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.0627

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.0126

Gnomad4 SAS exome AF: 0.0845

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.126 AC: 19146 AN: 152068 Hom.: 1304 Cov.: 31 AF XY: 0.124 AC XY: 9187 AN XY: 74324

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0829

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.0845

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.112

Alfa AF: 0.129 Hom.: 165

Bravo AF: 0.122

Asia WGS AF: 0.0660 AC: 231 AN: 3478

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	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.6
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs12948553; hg19: chr17-41606711;