17-43528880-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.112

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 -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	UniProt
ETV4	NM_001079675.5	c.1231-137A>G		intron_variant		ENST00000319349.10

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34380 AN: 151956 Hom.: 4141 Cov.: 31

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

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.: 31 AF XY: 0.229 AC XY: 16996 AN XY: 74334

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

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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

Other links and lift over

dbSNP: rs55989313; hg19: chr17-41606248; COSMIC: COSV52251631; COSMIC: COSV52251631;