Genetic Variant ETS1:p.Ile270Leu (chr11-128484877-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001143820.2(ETS1):c.808A>C(p.Ile270Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I270V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ETS1
NM_001143820.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.37

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23505956).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
ETS1	NM_001143820.2	MANE Select	c.808A>C	p.Ile270Leu	missense	Exon 7 of 10	NP_001137292.1	P14921-3
ETS1	NM_005238.4		c.676A>C	p.Ile226Leu	missense	Exon 5 of 8	NP_005229.1	P14921-1
ETS1	NM_001330451.2		c.676A>C	p.Ile226Leu	missense	Exon 5 of 7	NP_001317380.1	P14921-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ETS1	ENST00000392668.8	TSL:1 MANE Select	c.808A>C	p.Ile270Leu	missense	Exon 7 of 10	ENSP00000376436.3	P14921-3
ETS1	ENST00000319397.7	TSL:1	c.676A>C	p.Ile226Leu	missense	Exon 5 of 8	ENSP00000324578.5	P14921-1
ETS1	ENST00000531611.5	TSL:1	c.676A>C	p.Ile226Leu	missense	Exon 5 of 7	ENSP00000435666.1	P14921-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

Eigen

Benign

-0.13

Eigen_PC

Benign

0.072

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.014

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

3.4

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.27

REVEL

Benign

0.10

Sift

Benign

0.33

Sift4G

Benign

0.81

Polyphen

0.028

Vest4

0.47

MutPred

0.38

Loss of phosphorylation at Y223 (P = 0.1563)

MVP

0.40

MPC

0.40

ClinPred

0.50

GERP RS

5.6

Varity_R

0.18

gMVP

0.29

Mutation Taster

=85/15

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over