3-186057024-C-A

Position:

• chr3-186057024-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004454.3(ETV5):​c.1209+51G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 1,581,972 control chromosomes in the GnomAD database, including 7,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (898 hom., cov: 32)
  • Exomes 𝑓: 0.050 (6749 hom.)
• Consequence: ETV5 NM_004454.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0380

Genes affected

ETV5 (HGNC:3494): (ETS variant transcription factor 5) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in cellular response to oxidative stress; negative regulation of transcription by RNA polymerase II; and positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 3-186057024-C-A is Benign according to our data. Variant chr3-186057024-C-A is described in ClinVar as [Benign]. Clinvar id is 1179924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETV5	NM_004454.3	c.1209+51G>T		intron_variant		ENST00000306376.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETV5	ENST00000306376.10	c.1209+51G>T		intron_variant		1	NM_004454.3	P1
ETV5	ENST00000434744.5	c.1209+51G>T		intron_variant		1		P1
ETV5	ENST00000433149.1	c.219-4893G>T		intron_variant, NMD_transcript_variant		5
ETV5	ENST00000480706.1	n.383+51G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0614 AC: 9335 AN: 152118 Hom.: 894 Cov.: 32

Gnomad AFR AF: 0.0306

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.0972

Gnomad FIN AF: 0.0905

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0278

Gnomad OTH AF: 0.0603

GnomAD3 exomes AF: 0.100 AC: 23770 AN: 236798 Hom.: 3019 AF XY: 0.0927 AC XY: 11895 AN XY: 128266

Gnomad AFR exome AF: 0.0291

Gnomad AMR exome AF: 0.236

Gnomad ASJ exome AF: 0.0266

Gnomad EAS exome AF: 0.455

Gnomad SAS exome AF: 0.0768

Gnomad FIN exome AF: 0.0918

Gnomad NFE exome AF: 0.0292

Gnomad OTH exome AF: 0.0804

GnomAD4 exome AF: 0.0498 AC: 71224 AN: 1429734 Hom.: 6749 Cov.: 29 AF XY: 0.0500 AC XY: 35370 AN XY: 707740

Gnomad4 AFR exome AF: 0.0303

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.0242

Gnomad4 EAS exome AF: 0.466

Gnomad4 SAS exome AF: 0.0767

Gnomad4 FIN exome AF: 0.0900

Gnomad4 NFE exome AF: 0.0249

Gnomad4 OTH exome AF: 0.0652

GnomAD4 genome AF: 0.0614 AC: 9348 AN: 152238 Hom.: 898 Cov.: 32 AF XY: 0.0683 AC XY: 5081 AN XY: 74418

Gnomad4 AFR AF: 0.0306

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.0977

Gnomad4 FIN AF: 0.0905

Gnomad4 NFE AF: 0.0278

Gnomad4 OTH AF: 0.0640

Alfa AF: 0.0370 Hom.: 58

Bravo AF: 0.0659

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	This variant is associated with the following publications: (PMID: 22771031) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.1
DANN	Benign	0.79

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: rs59852126; hg19: chr3-185774813;