Genetic Variant ETS1:c.*3297G>A (chr11-128459064-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001143820.2(ETS1):c.*3297G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.111 in 150,688 control chromosomes in the GnomAD database, including 1,135 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 0.11 ( 1134 hom., cov: 31)

Exomes 𝑓: 0.090 ( 1 hom. )

Consequence

ETS1
NM_001143820.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.92

Publications

63 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.21).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143820.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ETS1	NM_001143820.2	MANE Select	c.*3297G>A	3_prime_UTR	Exon 10 of 10	NP_001137292.1	P14921-3
ETS1	NM_005238.4		c.*3297G>A	3_prime_UTR	Exon 8 of 8	NP_005229.1	P14921-1
ETS1	NM_001330451.2		c.*3297G>A	3_prime_UTR	Exon 7 of 7	NP_001317380.1	P14921-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ETS1	ENST00000392668.8	TSL:1 MANE Select	c.*3297G>A	3_prime_UTR	Exon 10 of 10	ENSP00000376436.3	P14921-3
ETS1	ENST00000319397.7	TSL:1	c.*3297G>A	3_prime_UTR	Exon 8 of 8	ENSP00000324578.5	P14921-1
ETS1	ENST00000535549.5	TSL:1	c.*3297G>A	3_prime_UTR	Exon 4 of 4	ENSP00000441430.1	P14921-4

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16690

AN:

150128

Hom.:

1131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.0900

Gnomad ASJ

AF:

0.0639

Gnomad EAS

AF:

0.355

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.0943

Gnomad MID

AF:

0.0385

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0940

GnomAD4 exome

AF:

0.0897

AC:

AN:

446

Hom.:

Cov.:

AF XY:

0.0896

AC XY:

AN XY:

268

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.0455

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0933

AC:

AN:

418

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.111

AC:

16715

AN:

150242

Hom.:

1134

Cov.:

AF XY:

0.113

AC XY:

8278

AN XY:

73290

show subpopulations

African (AFR)

AF:

0.104

AC:

4247

AN:

40930

American (AMR)

AF:

0.0901

AC:

1363

AN:

15124

Ashkenazi Jewish (ASJ)

AF:

0.0639

AC:

221

AN:

3458

East Asian (EAS)

AF:

0.354

AC:

1818

AN:

5130

South Asian (SAS)

AF:

0.160

AC:

761

AN:

4758

European-Finnish (FIN)

AF:

0.0943

AC:

934

AN:

9904

Middle Eastern (MID)

AF:

0.0377

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.106

AC:

7148

AN:

67650

Other (OTH)

AF:

0.0944

AC:

197

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

714

1427

2141

2854

3568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.108

Hom.:

4109

Bravo

AF:

0.106

Asia WGS

AF:

0.208

AC:

713

AN:

3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

4.9

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over