chr11-128484933-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2

The NM_001143820.2(ETS1):​c.752C>T​(p.Ser251Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,613,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

ETS1
NM_001143820.2 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity ETS1_HUMAN
BP4
Computational evidence support a benign effect (MetaRNN=0.1665053).
BS2
High AC in GnomAdExome4 at 49 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ETS1NM_001143820.2 linkuse as main transcriptc.752C>T p.Ser251Leu missense_variant 7/10 ENST00000392668.8 NP_001137292.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ETS1ENST00000392668.8 linkuse as main transcriptc.752C>T p.Ser251Leu missense_variant 7/101 NM_001143820.2 ENSP00000376436 P14921-3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152112
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251140
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135712
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000335
AC:
49
AN:
1461616
Hom.:
0
Cov.:
31
AF XY:
0.0000371
AC XY:
27
AN XY:
727136
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000414
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152112
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74302
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 20, 2023The c.752C>T (p.S251L) alteration is located in exon 7 (coding exon 6) of the ETS1 gene. This alteration results from a C to T substitution at nucleotide position 752, causing the serine (S) at amino acid position 251 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.52
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.63
.;.;.;D
Eigen
Benign
-0.14
Eigen_PC
Benign
0.080
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.94
D;D;D;D
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.17
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.69
.;N;N;N
MutationTaster
Benign
0.63
D;D;D;D;D;D
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-2.3
N;D;N;N
REVEL
Benign
0.061
Sift
Benign
0.15
T;T;T;T
Sift4G
Benign
0.14
T;T;T;T
Polyphen
0.0
.;.;.;B
Vest4
0.37
MutPred
0.55
.;Loss of disorder (P = 0.0578);Loss of disorder (P = 0.0578);Loss of disorder (P = 0.0578);
MVP
0.36
MPC
0.34
ClinPred
0.33
T
GERP RS
5.7
Varity_R
0.11
gMVP
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1045241125; hg19: chr11-128354828; COSMIC: COSV60091363; COSMIC: COSV60091363; API