Variant 11-128485068-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001143820.2(ETS1):c.617A>G(p.Tyr206Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00316 in 1,609,420 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 10 hom. )

Consequence

ETS1
NM_001143820.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 6.24

Variant links:

Genes affected

ETS1 (HGNC:3488): (ETS proto-oncogene 1, transcription factor) This gene encodes a member of the ETS family of transcription factors, which are defined by the presence of a conserved ETS DNA-binding domain that recognizes the core consensus DNA sequence GGAA/T in target genes. These proteins function either as transcriptional activators or repressors of numerous genes, and are involved in stem cell development, cell senescence and death, and tumorigenesis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jul 2011]

ETS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012028724).

BS2

High AC in GnomAd4 at 337 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETS1	NM_001143820.2 linkuse as main transcript	c.617A>G	p.Tyr206Cys	missense_variant	7/10	ENST00000392668.8	NP_001137292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETS1	ENST00000392668.8 linkuse as main transcript	c.617A>G	p.Tyr206Cys	missense_variant	7/10	1	NM_001143820.2	ENSP00000376436		P14921-3

Frequencies

GnomAD3 genomes

AF:

0.00222

AC:

337

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00369

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00215

AC:

535

AN:

249310

Hom.:

AF XY:

0.00205

AC XY:

276

AN XY:

134684

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.000410

Gnomad ASJ exome

AF:

0.00201

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00204

Gnomad FIN exome

AF:

0.00125

Gnomad NFE exome

AF:

0.00349

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00325

AC:

4743

AN:

1457198

Hom.:

Cov.:

AF XY:

0.00321

AC XY:

2327

AN XY:

724136

show subpopulations

Gnomad4 AFR exome

AF:

0.000540

Gnomad4 AMR exome

AF:

0.000675

Gnomad4 ASJ exome

AF:

0.00173

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00186

Gnomad4 FIN exome

AF:

0.00197

Gnomad4 NFE exome

AF:

0.00376

Gnomad4 OTH exome

AF:

0.00357

GnomAD4 genome

AF:

0.00221

AC:

337

AN:

152222

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

162

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00369

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00296

Hom.:

Bravo

AF:

0.00190

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00227

AC:

275

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00333

EpiControl

AF:

0.00255

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Jun 11, 2015

- -

ETS1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 10, 2023

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

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

.;.;.;D

Eigen

Benign

0.16

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Benign

0.039

MetaRNN

Benign

0.012

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.7

.;L;L;L

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.025

D;T;D;D

Sift4G

Benign

0.14

T;T;D;T

Polyphen

0.0

.;.;.;B

Vest4

0.69

MVP

0.52

MPC

1.2

ClinPred

0.020

GERP RS

4.7

Varity_R

0.20

gMVP

0.81

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