11-128693941-CGAGA-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000281428.12(FLI1):​c.-638_-635delGAGA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0664 in 172,250 control chromosomes in the GnomAD database, including 138 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.060 ( 136 hom., cov: 0)
Exomes 𝑓: 0.073 ( 2 hom. )

Consequence

FLI1
ENST00000281428.12 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.710

Publications

0 publications found
Variant links:
Genes affected
FLI1 (HGNC:3749): (Fli-1 proto-oncogene, ETS transcription factor) This gene encodes a transcription factor containing an ETS DNA-binding domain. The gene can undergo a t(11;22)(q24;q12) translocation with the Ewing sarcoma gene on chromosome 22, which results in a fusion gene that is present in the majority of Ewing sarcoma cases. An acute lymphoblastic leukemia-associated t(4;11)(q21;q23) translocation involving this gene has also been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]
SENCR (HGNC:44177): (smooth muscle and endothelial cell enriched migration/differentiation-associated lncRNA)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6
Variant 11-128693941-CGAGA-C is Benign according to our data. Variant chr11-128693941-CGAGA-C is described in ClinVar as [Benign]. Clinvar id is 1235009.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FLI1NM_002017.5 linkc.-317_-314delGAGA upstream_gene_variant ENST00000527786.7 NP_002008.2 Q01543-1A0A024R3M5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FLI1ENST00000527786.7 linkc.-317_-314delGAGA upstream_gene_variant 1 NM_002017.5 ENSP00000433488.2 Q01543-1

Frequencies

GnomAD3 genomes
AF:
0.0596
AC:
4921
AN:
82514
Hom.:
137
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0680
Gnomad AMI
AF:
0.0618
Gnomad AMR
AF:
0.108
Gnomad ASJ
AF:
0.0435
Gnomad EAS
AF:
0.0347
Gnomad SAS
AF:
0.0414
Gnomad FIN
AF:
0.0632
Gnomad MID
AF:
0.0571
Gnomad NFE
AF:
0.0508
Gnomad OTH
AF:
0.0536
GnomAD4 exome
AF:
0.0727
AC:
6523
AN:
89714
Hom.:
2
AF XY:
0.0701
AC XY:
2987
AN XY:
42610
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.0904
AC:
340
AN:
3760
American (AMR)
AF:
0.120
AC:
310
AN:
2588
Ashkenazi Jewish (ASJ)
AF:
0.0758
AC:
388
AN:
5122
East Asian (EAS)
AF:
0.0691
AC:
767
AN:
11104
South Asian (SAS)
AF:
0.0269
AC:
47
AN:
1750
European-Finnish (FIN)
AF:
0.0360
AC:
71
AN:
1974
Middle Eastern (MID)
AF:
0.0664
AC:
36
AN:
542
European-Non Finnish (NFE)
AF:
0.0719
AC:
4010
AN:
55808
Other (OTH)
AF:
0.0784
AC:
554
AN:
7066
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.312
Heterozygous variant carriers
0
426
852
1278
1704
2130
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
22
44
66
88
110
<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:
0.0596
AC:
4920
AN:
82536
Hom.:
136
Cov.:
0
AF XY:
0.0610
AC XY:
2321
AN XY:
38030
show subpopulations
African (AFR)
AF:
0.0679
AC:
1246
AN:
18344
American (AMR)
AF:
0.108
AC:
840
AN:
7786
Ashkenazi Jewish (ASJ)
AF:
0.0435
AC:
108
AN:
2480
East Asian (EAS)
AF:
0.0349
AC:
94
AN:
2696
South Asian (SAS)
AF:
0.0417
AC:
88
AN:
2110
European-Finnish (FIN)
AF:
0.0632
AC:
200
AN:
3166
Middle Eastern (MID)
AF:
0.0672
AC:
9
AN:
134
European-Non Finnish (NFE)
AF:
0.0508
AC:
2238
AN:
44086
Other (OTH)
AF:
0.0531
AC:
62
AN:
1168
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.437
Heterozygous variant carriers
0
158
316
473
631
789
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
46
92
138
184
230
<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:
0.00
Hom.:
0

ClinVar

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

Submissions by phenotype

not provided Benign:1
Jun 20, 2021
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.71
Mutation Taster
=99/1
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: rs57930585; hg19: chr11-128563836; API