chr17-43545844-G-A

Variant names:

• chr17-43545844-G-A
• rs79158595
• NM_001079675.5:c.-51-176C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001079675.5(ETV4):​c.-51-176C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 598,508 control chromosomes in the GnomAD database, including 27,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5555 hom., cov: 32)
  • Exomes 𝑓: 0.31 (21611 hom.)
• Consequence: ETV4 NM_001079675.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.360
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 17-43545844-G-A is Benign according to our data. Variant chr17-43545844-G-A is described in ClinVar as Benign. ClinVar VariationId is 1256771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV4	NM_001079675.5	MANE Select	c.-51-176C>T		intron	N/A	NP_001073143.1
	ETV4	NM_001369366.2		c.-116C>T		5_prime_UTR	Exon 1 of 13	NP_001356295.1
	ETV4	NM_001986.4		c.-52+17C>T		intron	N/A	NP_001977.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV4	ENST00000319349.10	TSL:1 MANE Select	c.-51-176C>T		intron	N/A	ENSP00000321835.4
	ETV4	ENST00000591713.5	TSL:1	c.-52+17C>T		intron	N/A	ENSP00000465718.1
	ETV4	ENST00000538265.5	TSL:2	c.-58+17C>T		intron	N/A	ENSP00000443846.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38416 AN: 151854 Hom.: 5555 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.306 AC: 136844 AN: 446534 Hom.: 21611 Cov.: 3 AF XY: 0.307 AC XY: 72485 AN XY: 236436

African (AFR) AF: 0.115 AC: 1368 AN: 11904

American (AMR) AF: 0.235 AC: 4343 AN: 18450

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 3884 AN: 13420

East Asian (EAS) AF: 0.371 AC: 11350 AN: 30628

South Asian (SAS) AF: 0.282 AC: 12900 AN: 45788

European-Finnish (FIN) AF: 0.378 AC: 11059 AN: 29234

Middle Eastern (MID) AF: 0.300 AC: 588 AN: 1962

European-Non Finnish (NFE) AF: 0.312 AC: 84156 AN: 269302

Other (OTH) AF: 0.278 AC: 7196 AN: 25846

GnomAD4 genome AF: 0.253 AC: 38417 AN: 151974 Hom.: 5555 Cov.: 32 AF XY: 0.256 AC XY: 19027 AN XY: 74262

African (AFR) AF: 0.111 AC: 4624 AN: 41508

American (AMR) AF: 0.228 AC: 3482 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1028 AN: 3472

East Asian (EAS) AF: 0.319 AC: 1629 AN: 5114

South Asian (SAS) AF: 0.276 AC: 1331 AN: 4824

European-Finnish (FIN) AF: 0.391 AC: 4117 AN: 10526

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

European-Non Finnish (NFE) AF: 0.314 AC: 21315 AN: 67918

Other (OTH) AF: 0.250 AC: 528 AN: 2112

Alfa AF: 0.253 Hom.: 787

Bravo AF: 0.234

Asia WGS AF: 0.218 AC: 758 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Benign	0.85
PhyloP100		0.36
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs79158595; hg19: chr17-41623212;