chr17-43546302-C-T

Variant names:

• chr17-43546302-C-T
• rs3765174
• NM_001079675.5:c.-169G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079675.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV4	NM_001079675.5	MANE Select	c.-169G>A		5_prime_UTR	Exon 1 of 13	NP_001073143.1	P43268-1
	ETV4	NM_001261437.3		c.-175G>A		5_prime_UTR	Exon 1 of 12	NP_001248366.1	P43268-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV4	ENST00000319349.10	TSL:1 MANE Select	c.-169G>A		5_prime_UTR	Exon 1 of 13	ENSP00000321835.4	P43268-1
	ETV4	ENST00000922774.1		c.-169G>A		5_prime_UTR	Exon 1 of 13	ENSP00000592833.1
	ETV4	ENST00000922776.1		c.-169G>A		5_prime_UTR	Exon 1 of 13	ENSP00000592835.1

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

African (AFR) AF: 0.167 AC: 1 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.300 AC: 3 AN: 10

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.260 AC: 40 AN: 154

Other (OTH) AF: 0.167 AC: 2 AN: 12

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

African (AFR) AF: 0.111 AC: 4620 AN: 41488

American (AMR) AF: 0.227 AC: 3478 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1025 AN: 3472

East Asian (EAS) AF: 0.317 AC: 1618 AN: 5112

South Asian (SAS) AF: 0.275 AC: 1325 AN: 4810

European-Finnish (FIN) AF: 0.391 AC: 4133 AN: 10564

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21289 AN: 67876

Other (OTH) AF: 0.250 AC: 526 AN: 2108

Alfa AF: 0.273 Hom.: 1011

Bravo AF: 0.234

Asia WGS AF: 0.220 AC: 764 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.93
PhyloP100		0.33
PromoterAI		0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=294/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3765174; hg19: chr17-41623670;