chr17-43530635-T-A

Position:

• chr17-43530635-T-A

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.812-454A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 149,760 control chromosomes in the GnomAD database, including 10,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (10811 hom., cov: 31)
• Consequence: ETV4 NM_001079675.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.91

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=-0.89).
• BP6: Variant 17-43530635-T-A is Benign according to our data. Variant chr17-43530635-T-A is described in ClinVar as [Benign]. Clinvar id is 1241567.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETV4	NM_001079675.5	c.812-454A>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.812-454A>T		intron_variant		1	NM_001079675.5	ENSP00000321835	P1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 51261 AN: 149642 Hom.: 10809 Cov.: 31

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.342 AC: 51259 AN: 149760 Hom.: 10811 Cov.: 31 AF XY: 0.342 AC XY: 24970 AN XY: 73056

Gnomad4 AFR AF: 0.0848

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.379

Alfa AF: 0.394 Hom.: 1640

Bravo AF: 0.322

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	-0.89
CADD	Benign	0.0050
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11652592; hg19: chr17-41608003;