Genetic Variant FLI1:c.-640_-635delGAGAGA (chr11-128693941-CGAGAGA-C) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The ENST00000281428.12(FLI1):c.-640_-635delGAGAGA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 172,806 control chromosomes in the GnomAD database, including 383 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 378 hom., cov: 0)

Exomes 𝑓: 0.11 ( 5 hom. )

Consequence

FLI1
ENST00000281428.12 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.49

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]

FLI1 links:

SENCR (HGNC:44177): (smooth muscle and endothelial cell enriched migration/differentiation-associated lncRNA)

SENCR links:

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-CGAGAGA-C is Benign according to our data. Variant chr11-128693941-CGAGAGA-C is described in ClinVar as [Benign]. Clinvar id is 1280517.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLI1	NM_002017.5 link	c.-317_-312delGAGAGA		upstream_gene_variant		ENST00000527786.7	NP_002008.2	Q01543-1A0A024R3M5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLI1	ENST00000527786.7 link	c.-317_-312delGAGAGA		upstream_gene_variant		1	NM_002017.5	ENSP00000433488.2		Q01543-1

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

9095

AN:

82508

Hom.:

377

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.0883

Gnomad AMR

AF:

0.0792

Gnomad ASJ

AF:

0.0990

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.0714

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.103

GnomAD4 exome

AF:

0.112

AC:

10141

AN:

90276

Hom.:

AF XY:

0.110

AC XY:

4717

AN XY:

42812

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.118

AC:

449

AN:

3810

American (AMR)

AF:

0.111

AC:

295

AN:

2656

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

543

AN:

5152

East Asian (EAS)

AF:

0.122

AC:

1362

AN:

11154

South Asian (SAS)

AF:

0.0608

AC:

105

AN:

1726

European-Finnish (FIN)

AF:

0.0813

AC:

160

AN:

1968

Middle Eastern (MID)

AF:

0.121

AC:

AN:

552

European-Non Finnish (NFE)

AF:

0.113

AC:

6331

AN:

56112

Other (OTH)

AF:

0.116

AC:

829

AN:

7146

⚠️ 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: 0.333

Heterozygous variant carriers

594

1187

1781

2374

2968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.110

AC:

9096

AN:

82530

Hom.:

378

Cov.:

AF XY:

0.109

AC XY:

4143

AN XY:

38054

show subpopulations

African (AFR)

AF:

0.109

AC:

2001

AN:

18398

American (AMR)

AF:

0.0790

AC:

617

AN:

7806

Ashkenazi Jewish (ASJ)

AF:

0.0990

AC:

245

AN:

2474

East Asian (EAS)

AF:

0.117

AC:

316

AN:

2698

South Asian (SAS)

AF:

0.118

AC:

249

AN:

2108

European-Finnish (FIN)

AF:

0.142

AC:

450

AN:

3174

Middle Eastern (MID)

AF:

0.0746

AC:

AN:

134

European-Non Finnish (NFE)

AF:

0.115

AC:

5039

AN:

43998

Other (OTH)

AF:

0.101

AC:

119

AN:

1174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

292

584

875

1167

1459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 19, 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

2.5

Mutation Taster

=297/3

polymorphism (auto)

(source)

Splicing

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.

11-128693941-CGAGAGA-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over