11-128489374-C-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001143820.2(ETS1):​c.451G>A​(p.Ala151Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00393 in 1,614,178 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0041 ( 18 hom. )

Consequence

ETS1
NM_001143820.2 missense

Scores

1
6
12

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.02

Publications

10 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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.012863308).
BP6
Variant 11-128489374-C-T is Benign according to our data. Variant chr11-128489374-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 779438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 369 Unknown,AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ETS1NM_001143820.2 linkc.451G>A p.Ala151Thr missense_variant Exon 5 of 10 ENST00000392668.8 NP_001137292.1 P14921-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ETS1ENST00000392668.8 linkc.451G>A p.Ala151Thr missense_variant Exon 5 of 10 1 NM_001143820.2 ENSP00000376436.3 P14921-3

Frequencies

GnomAD3 genomes
AF:
0.00243
AC:
370
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000892
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00157
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000828
Gnomad FIN
AF:
0.000659
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00431
Gnomad OTH
AF:
0.00240
GnomAD2 exomes
AF:
0.00215
AC:
541
AN:
251382
AF XY:
0.00230
show subpopulations
Gnomad AFR exome
AF:
0.000554
Gnomad AMR exome
AF:
0.000925
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.0000544
Gnomad FIN exome
AF:
0.000323
Gnomad NFE exome
AF:
0.00400
Gnomad OTH exome
AF:
0.00179
GnomAD4 exome
AF:
0.00409
AC:
5974
AN:
1461862
Hom.:
18
Cov.:
32
AF XY:
0.00397
AC XY:
2889
AN XY:
727240
show subpopulations
African (AFR)
AF:
0.000717
AC:
24
AN:
33480
American (AMR)
AF:
0.00101
AC:
45
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.000115
AC:
3
AN:
26136
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39700
South Asian (SAS)
AF:
0.000927
AC:
80
AN:
86258
European-Finnish (FIN)
AF:
0.000580
AC:
31
AN:
53420
Middle Eastern (MID)
AF:
0.000693
AC:
4
AN:
5768
European-Non Finnish (NFE)
AF:
0.00502
AC:
5579
AN:
1111984
Other (OTH)
AF:
0.00343
AC:
207
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.456
Heterozygous variant carriers
0
307
614
920
1227
1534
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
218
436
654
872
1090
<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:
0.00242
AC:
369
AN:
152316
Hom.:
0
Cov.:
32
AF XY:
0.00218
AC XY:
162
AN XY:
74470
show subpopulations
African (AFR)
AF:
0.000890
AC:
37
AN:
41580
American (AMR)
AF:
0.00157
AC:
24
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5186
South Asian (SAS)
AF:
0.000621
AC:
3
AN:
4828
European-Finnish (FIN)
AF:
0.000659
AC:
7
AN:
10618
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00431
AC:
293
AN:
68016
Other (OTH)
AF:
0.00237
AC:
5
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
19
37
56
74
93
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
10
20
30
40
50
<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:
0.00345
Hom.:
0
Bravo
AF:
0.00252
TwinsUK
AF:
0.00566
AC:
21
ALSPAC
AF:
0.00571
AC:
22
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00431
AC:
37
ExAC
AF:
0.00231
AC:
280
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.00403
EpiControl
AF:
0.00391

ClinVar

Significance: Likely 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:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.39
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.39
.;.;.;T
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.88
D;D;D;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.013
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.0
.;M;M;M
PhyloP100
4.0
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-0.90
N;N;N;N
REVEL
Benign
0.11
Sift
Benign
0.32
T;T;T;T
Sift4G
Benign
0.56
T;T;T;T
Polyphen
0.47
.;.;.;P
Vest4
0.52
MVP
0.53
MPC
0.48
ClinPred
0.022
T
GERP RS
5.6
Varity_R
0.13
gMVP
0.56
Mutation Taster
=44/56
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs79963544; hg19: chr11-128359269; COSMIC: COSV60091531; COSMIC: COSV60091531; API