Genetic Variant ETS1:c.*1736A>G (chr11-128460625-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001143820.2(ETS1):c.*1736A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,158 control chromosomes in the GnomAD database, including 17,028 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 17011 hom., cov: 31)

Exomes 𝑓: 0.51 ( 17 hom. )

Consequence

ETS1
NM_001143820.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.491

Publications

32 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETS1	NM_001143820.2 link	c.*1736A>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000392668.8	NP_001137292.1	P14921-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ETS1	ENST00000392668.8 link	c.*1736A>G	3_prime_UTR_variant	Exon 10 of 10	1	NM_001143820.2	ENSP00000376436.3	P14921-3
ETS1	ENST00000319397.7 link	c.*1736A>G	3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000324578.5	P14921-1
ETS1	ENST00000535549.5 link	c.*1736A>G	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000441430.1	P14921-4
ETS1	ENST00000526145.6 link	c.*1736A>G	3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000433500.1	P14921-2

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69672

AN:

151898

Hom.:

17011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.289

Gnomad AMI

AF:

0.514

Gnomad AMR

AF:

0.427

Gnomad ASJ

AF:

0.581

Gnomad EAS

AF:

0.564

Gnomad SAS

AF:

0.553

Gnomad FIN

AF:

0.590

Gnomad MID

AF:

0.630

Gnomad NFE

AF:

0.525

Gnomad OTH

AF:

0.485

GnomAD4 exome

AF:

0.514

AC:

AN:

142

Hom.:

Cov.:

AF XY:

0.487

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.507

AC:

AN:

136

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.458

AC:

69678

AN:

152016

Hom.:

17011

Cov.:

AF XY:

0.462

AC XY:

34356

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.289

AC:

11972

AN:

41468

American (AMR)

AF:

0.426

AC:

6521

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.581

AC:

2015

AN:

3470

East Asian (EAS)

AF:

0.565

AC:

2914

AN:

5162

South Asian (SAS)

AF:

0.552

AC:

2663

AN:

4826

European-Finnish (FIN)

AF:

0.590

AC:

6206

AN:

10520

Middle Eastern (MID)

AF:

0.616

AC:

181

AN:

294

European-Non Finnish (NFE)

AF:

0.525

AC:

35703

AN:

67962

Other (OTH)

AF:

0.490

AC:

1036

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1813

3626

5438

7251

9064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.500

Hom.:

32688

Bravo

AF:

0.440

Asia WGS

AF:

0.578

AC:

2011

AN:

3478

ClinVar

Significance: 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:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 16, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 31275358) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.6

(source)

DANN

Benign

0.88

PhyloP100

0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr11-128460625-T-C

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