11-128486082-C-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001143820.2(ETS1):​c.600G>A​(p.Ser200Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,607,380 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0026 ( 73 hom. )

Consequence

ETS1
NM_001143820.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.888

Publications

4 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 -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.21).
BP6
Variant 11-128486082-C-T is Benign according to our data. Variant chr11-128486082-C-T is described in ClinVar as [Benign]. Clinvar id is 777426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.888 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00198 (301/152052) while in subpopulation SAS AF = 0.0357 (172/4816). AF 95% confidence interval is 0.0314. There are 2 homozygotes in GnomAd4. There are 192 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High AC in GnomAd4 at 301 Unknown,AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ETS1NM_001143820.2 linkc.600G>A p.Ser200Ser synonymous_variant Exon 6 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.600G>A p.Ser200Ser synonymous_variant Exon 6 of 10 1 NM_001143820.2 ENSP00000376436.3 P14921-3

Frequencies

GnomAD3 genomes
AF:
0.00198
AC:
301
AN:
151934
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00112
Gnomad ASJ
AF:
0.00980
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0357
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00101
Gnomad OTH
AF:
0.00144
GnomAD2 exomes
AF:
0.00471
AC:
1183
AN:
251168
AF XY:
0.00633
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000550
Gnomad ASJ exome
AF:
0.00526
Gnomad EAS exome
AF:
0.0000544
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000951
Gnomad OTH exome
AF:
0.00294
GnomAD4 exome
AF:
0.00258
AC:
3749
AN:
1455328
Hom.:
73
Cov.:
28
AF XY:
0.00356
AC XY:
2581
AN XY:
724542
show subpopulations
African (AFR)
AF:
0.000240
AC:
8
AN:
33330
American (AMR)
AF:
0.000470
AC:
21
AN:
44676
Ashkenazi Jewish (ASJ)
AF:
0.00556
AC:
145
AN:
26092
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39644
South Asian (SAS)
AF:
0.0321
AC:
2759
AN:
86028
European-Finnish (FIN)
AF:
0.0000187
AC:
1
AN:
53402
Middle Eastern (MID)
AF:
0.00730
AC:
42
AN:
5754
European-Non Finnish (NFE)
AF:
0.000541
AC:
598
AN:
1106228
Other (OTH)
AF:
0.00291
AC:
175
AN:
60174
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.467
Heterozygous variant carriers
0
163
326
489
652
815
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
52
104
156
208
260
<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:
0.00198
AC:
301
AN:
152052
Hom.:
2
Cov.:
32
AF XY:
0.00258
AC XY:
192
AN XY:
74328
show subpopulations
African (AFR)
AF:
0.000145
AC:
6
AN:
41462
American (AMR)
AF:
0.00111
AC:
17
AN:
15258
Ashkenazi Jewish (ASJ)
AF:
0.00980
AC:
34
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5186
South Asian (SAS)
AF:
0.0357
AC:
172
AN:
4816
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10564
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00101
AC:
69
AN:
67986
Other (OTH)
AF:
0.00142
AC:
3
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
14
28
42
56
70
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
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:
0.00131
Hom.:
0
Bravo
AF:
0.000971
Asia WGS
AF:
0.00982
AC:
34
AN:
3478
EpiCase
AF:
0.00158
EpiControl
AF:
0.00101

ClinVar

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

- -

Jul 31, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.21
CADD
Benign
16
DANN
Benign
0.66
PhyloP100
0.89
Mutation Taster
=86/14
polymorphism

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

Other links and lift over

dbSNP: rs149636924; hg19: chr11-128355977; API