Genetic Variant ENST00000281428.12:c.-652_-635delGAGAGAGAGAGAGAGAGA (chr11-128693941-CGAGAGAGAGAGAGAGAGA-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.-652_-635delGAGAGAGAGAGAGAGAGA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 176,490 control chromosomes in the GnomAD database, including 1,846 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.24 ( 1762 hom., cov: 0)

Exomes 𝑓: 0.18 ( 84 hom. )

Consequence

FLI1
ENST00000281428.12 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.85

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-CGAGAGAGAGAGAGAGAGA-C is Benign according to our data. Variant chr11-128693941-CGAGAGAGAGAGAGAGAGA-C is described in ClinVar as [Benign]. Clinvar id is 1284178.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLI1	NM_002017.5 link	c.-317_-300delGAGAGAGAGAGAGAGAGA		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_-300delGAGAGAGAGAGAGAGAGA		upstream_gene_variant		1	NM_002017.5	ENSP00000433488.2		Q01543-1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

19605

AN:

82940

Hom.:

1759

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.414

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.267

GnomAD4 exome

AF:

0.181

AC:

16893

AN:

93526

Hom.:

AF XY:

0.184

AC XY:

8170

AN XY:

44408

show subpopulations

African (AFR)

AF:

0.106

AC:

416

AN:

3920

American (AMR)

AF:

0.123

AC:

338

AN:

2742

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

1226

AN:

5344

East Asian (EAS)

AF:

0.124

AC:

1437

AN:

11570

South Asian (SAS)

AF:

0.0705

AC:

125

AN:

1772

European-Finnish (FIN)

AF:

0.209

AC:

415

AN:

1990

Middle Eastern (MID)

AF:

0.229

AC:

131

AN:

572

European-Non Finnish (NFE)

AF:

0.197

AC:

11443

AN:

58226

Other (OTH)

AF:

0.184

AC:

1362

AN:

7390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.421

Heterozygous variant carriers

599

1197

1796

2394

2993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.236

AC:

19609

AN:

82964

Hom.:

1762

Cov.:

AF XY:

0.236

AC XY:

9030

AN XY:

38260

show subpopulations

African (AFR)

AF:

0.156

AC:

2882

AN:

18444

American (AMR)

AF:

0.218

AC:

1709

AN:

7852

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

848

AN:

2484

East Asian (EAS)

AF:

0.238

AC:

644

AN:

2704

South Asian (SAS)

AF:

0.206

AC:

437

AN:

2118

European-Finnish (FIN)

AF:

0.235

AC:

749

AN:

3194

Middle Eastern (MID)

AF:

0.410

AC:

AN:

134

European-Non Finnish (NFE)

AF:

0.267

AC:

11835

AN:

44292

Other (OTH)

AF:

0.270

AC:

316

AN:

1170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.560

Heterozygous variant carriers

665

1330

1994

2659

3324

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

2.9

Mutation Taster

=90/10

polymorphism (auto)

(source)

Splicing

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

Publications

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ENST00000281428.12:c.-652_-635delGAGAGAGAGAGAGAGAGA

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