chr17-43530609-C-T

Position:

• chr17-43530609-C-T

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.812-428G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 118,914 control chromosomes in the GnomAD database, including 6,301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (6301 hom., cov: 26)
• Consequence: ETV4 NM_001079675.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.03

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-43530609-C-T is Benign according to our data. Variant chr17-43530609-C-T is described in ClinVar as [Benign]. Clinvar id is 1257943.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETV4	NM_001079675.5	c.812-428G>A		intron_variant		ENST00000319349.10	NP_001073143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETV4	ENST00000319349.10	c.812-428G>A		intron_variant		1	NM_001079675.5	ENSP00000321835	P1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 43281 AN: 118840 Hom.: 6288 Cov.: 26

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.407

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.341

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.364 AC: 43314 AN: 118914 Hom.: 6301 Cov.: 26 AF XY: 0.363 AC XY: 21183 AN XY: 58294

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.346

Alfa AF: 0.315 Hom.: 408

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

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.70
DANN	Benign	0.88

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: rs11658920; hg19: chr17-41607977;