11-128489374-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001143820.2(ETS1):c.451G>A(p.Ala151Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00393 in 1,614,178 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 18 hom. )

Consequence

ETS1
NM_001143820.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.02

Publications

10 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012863308).

BP6

Variant 11-128489374-C-T is Benign according to our data. Variant chr11-128489374-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 779438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 369 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETS1	NM_001143820.2 link	c.451G>A	p.Ala151Thr	missense_variant	Exon 5 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.451G>A	p.Ala151Thr	missense_variant	Exon 5 of 10	1	NM_001143820.2	ENSP00000376436.3		P14921-3

Frequencies

GnomAD3 genomes

AF:

0.00243

AC:

370

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000892

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00431

Gnomad OTH

AF:

0.00240

GnomAD2 exomes

AF:

0.00215

AC:

541

AN:

251382

AF XY:

0.00230

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000925

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.00400

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00409

AC:

5974

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00397

AC XY:

2889

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.000717

AC:

AN:

33480

American (AMR)

AF:

0.00101

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000927

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000580

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00502

AC:

5579

AN:

1111984

Other (OTH)

AF:

0.00343

AC:

207

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

307

614

920

1227

1534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00242

AC:

369

AN:

152316

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

162

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.000890

AC:

AN:

41580

American (AMR)

AF:

0.00157

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000659

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00431

AC:

293

AN:

68016

Other (OTH)

AF:

0.00237

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00345

Hom.:

Bravo

AF:

0.00252

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00431

AC:

ExAC

AF:

0.00231

AC:

280

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00403

EpiControl

AF:

0.00391

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

.;.;.;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.013

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

.;M;M;M

PhyloP100

4.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.90

N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.32

T;T;T;T

Sift4G

Benign

0.56

T;T;T;T

Polyphen

0.47

.;.;.;P

Vest4

0.52

MVP

0.53

MPC

0.48

ClinPred

0.022

GERP RS

5.6

Varity_R

0.13

gMVP

0.56

Mutation Taster

=44/56

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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11-128489374-C-T

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