Genetic Variant ETV3L:p.Glu311Glu (chr1-157092802-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001004341.2(ETV3L):c.933A>G(p.Glu311Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 1,614,144 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 5 hom. )

Consequence

ETV3L
NM_001004341.2 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.127

Variant links:

Genes affected

ETV3L (HGNC:33834): (ETS variant transcription factor 3 like) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in cell differentiation and regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ETV3L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 1-157092802-T-C is Benign according to our data. Variant chr1-157092802-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3055606.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.127 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETV3L	NM_001004341.2 link	c.933A>G	p.Glu311Glu	synonymous_variant	Exon 5 of 5	ENST00000454449.3	NP_001004341.1	Q6ZN32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ETV3L	ENST00000454449.3 link	c.933A>G	p.Glu311Glu	synonymous_variant	Exon 5 of 5	2	NM_001004341.2	ENSP00000430271.1	Q6ZN32
ETV3L	ENST00000671886.1 link	c.933A>G	p.Glu311Glu	synonymous_variant	Exon 6 of 6			ENSP00000500322.1	Q6ZN32
ETV3L	ENST00000671942.1 link	c.933A>G	p.Glu311Glu	synonymous_variant	Exon 6 of 6			ENSP00000500028.1	Q6ZN32
ETV3L	ENST00000672100.1 link	c.933A>G	p.Glu311Glu	synonymous_variant	Exon 6 of 6			ENSP00000500154.1	Q6ZN32

Frequencies

GnomAD3 genomes

AF:

0.00239

AC:

364

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00453

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00243

AC:

610

AN:

251418

Hom.:

AF XY:

0.00241

AC XY:

328

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00152

Gnomad NFE exome

AF:

0.00454

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00298

AC:

4360

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00294

AC XY:

2138

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00180

Gnomad4 NFE exome

AF:

0.00366

Gnomad4 OTH exome

AF:

0.00209

GnomAD4 genome

AF:

0.00239

AC:

364

AN:

152272

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

157

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00453

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00314

Hom.:

Bravo

AF:

0.00246

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00273

EpiControl

AF:

0.00308

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ETV3L-related disorder

Benign:1

Dec 13, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

3.9

DANN

Benign

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over