Genetic Variant ETS1:c.214+19748T>C (chr11-128536543-A-G) – 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.214+19748T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,056 control chromosomes in the GnomAD database, including 18,660 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 0.49 ( 18660 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

ETS1
NM_001143820.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0160

Publications

26 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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.684 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETS1	NM_001143820.2	MANE Select	c.214+19748T>C		intron	N/A	NP_001137292.1	P14921-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ETS1	ENST00000392668.8	TSL:1 MANE Select	c.214+19748T>C	intron	N/A	ENSP00000376436.3	P14921-3
ETS1	ENST00000900294.1		c.214+19748T>C	intron	N/A	ENSP00000570353.1
ETS1	ENST00000917573.1		c.214+19748T>C	intron	N/A	ENSP00000587632.1

Frequencies

GnomAD3 genomes

AF:

0.486

AC:

73807

AN:

151938

Hom.:

18654

Cov.:

show subpopulations

Gnomad AFR

AF:

0.358

Gnomad AMI

AF:

0.402

Gnomad AMR

AF:

0.560

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.703

Gnomad SAS

AF:

0.619

Gnomad FIN

AF:

0.562

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.513

Gnomad OTH

AF:

0.470

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.486

AC:

73845

AN:

152056

Hom.:

18660

Cov.:

AF XY:

0.495

AC XY:

36812

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.358

AC:

14831

AN:

41464

American (AMR)

AF:

0.560

AC:

8548

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

1554

AN:

3472

East Asian (EAS)

AF:

0.703

AC:

3642

AN:

5178

South Asian (SAS)

AF:

0.618

AC:

2987

AN:

4830

European-Finnish (FIN)

AF:

0.562

AC:

5932

AN:

10560

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.513

AC:

34889

AN:

67982

Other (OTH)

AF:

0.470

AC:

990

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1880

3761

5641

7522

9402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

676

1352

2028

2704

3380

<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:

0.461

Hom.:

7473

Bravo

AF:

0.474

Asia WGS

AF:

0.577

AC:

2004

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.8

(source)

DANN

Benign

0.82

PhyloP100

-0.016

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over