NM_001143820.2:c.617A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

congenital heart disease
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ETS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

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

BS2

High AC in GnomAd4 at 337 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETS1	NM_001143820.2 link	c.617A>G	p.Tyr206Cys	missense_variant	Exon 7 of 10	ENST00000392668.8	NP_001137292.1	P14921-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETS1	ENST00000392668.8 link	c.617A>G	p.Tyr206Cys	missense_variant	Exon 7 of 10	1	NM_001143820.2	ENSP00000376436.3		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

GnomAD2 exomes

AF:

0.00215

AC:

535

AN:

249310

AF XY:

0.00205

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 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

African (AFR)

AF:

0.000540

AC:

AN:

33338

American (AMR)

AF:

0.000675

AC:

AN:

44440

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

26010

East Asian (EAS)

AF:

0.00

AC:

AN:

39556

South Asian (SAS)

AF:

0.00186

AC:

160

AN:

85958

European-Finnish (FIN)

AF:

0.00197

AC:

105

AN:

53350

Middle Eastern (MID)

AF:

0.000871

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00376

AC:

4165

AN:

1108596

Other (OTH)

AF:

0.00357

AC:

215

AN:

60208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

222

443

665

886

1108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00221

AC:

337

AN:

152222

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

162

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.000794

AC:

AN:

41552

American (AMR)

AF:

0.000719

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00228

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00369

AC:

251

AN:

67994

Other (OTH)

AF:

0.00143

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00317

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

Jun 11, 2015

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

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ETS1-related disorder

Benign:1

Mar 10, 2023

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

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

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

PhyloP100

6.2

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

Mutation Taster

=94/6

polymorphism

(source)

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

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NM_001143820.2:c.617A>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over