rs11650719

Positions:

• chr17-43574517-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000586764.1(ETV4):​c.-169+4775C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,154 control chromosomes in the GnomAD database, including 1,977 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 0.15 (1977 hom., cov: 32)
• Consequence: ETV4 ENST00000586764.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146

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]

(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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.43574517G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETV4	ENST00000586764.1	c.-169+4775C>T		intron_variant		3		ENSP00000466673.1
DHX8	ENST00000588996.1	n.32-15571G>A		intron_variant		4
DHX8	ENST00000650571.1	n.*426-15571G>A		intron_variant				ENSP00000496923.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23092 AN: 152036 Hom.: 1976 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.00923

Gnomad SAS AF: 0.0816

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.152 AC: 23110 AN: 152154 Hom.: 1977 Cov.: 32 AF XY: 0.148 AC XY: 11015 AN XY: 74388

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.0926

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.00926

Gnomad4 SAS AF: 0.0803

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.139

Alfa AF: 0.142 Hom.: 721

Bravo AF: 0.149

Asia WGS AF: 0.0650 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11650719; hg19: chr17-41651885;