chr17-43546302-C-T

Position:

• chr17-43546302-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001079675.5(ETV4):​c.-169G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,120 control chromosomes in the GnomAD database, including 5,548 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (5542 hom., cov: 31)
  • Exomes 𝑓: 0.24 (6 hom.)
• Consequence: ETV4 NM_001079675.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328

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 (HGNC:):

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 -8 ACMG points.

• 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.-169G>A		5_prime_UTR_variant	1/13	ENST00000319349.10	NP_001073143.1
ETV4	NM_001261437.3	c.-175G>A		5_prime_UTR_variant	1/12		NP_001248366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETV4	ENST00000319349.10	c.-169G>A		5_prime_UTR_variant	1/13	1	NM_001079675.5	ENSP00000321835.4

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38376 AN: 151804 Hom.: 5542 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.253

GnomAD4 exome AF: 0.245 AC: 48 AN: 196 Hom.: 6 Cov.: 0 AF XY: 0.284 AC XY: 38 AN XY: 134

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.253 AC: 38377 AN: 151924 Hom.: 5542 Cov.: 31 AF XY: 0.256 AC XY: 19009 AN XY: 74240

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.250

Alfa AF: 0.277 Hom.: 1006

Bravo AF: 0.234

Asia WGS AF: 0.220 AC: 764 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.32		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3765174; hg19: chr17-41623670;