Genetic Variant FLI1:c.-644_-635delGAGAGAGAGA (chr11-128693941-CGAGAGAGAGA-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.-644_-635delGAGAGAGAGA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 174,890 control chromosomes in the GnomAD database, including 210 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.076 ( 205 hom., cov: 0)

Exomes 𝑓: 0.069 ( 5 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:

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ACMG classification

Classification was made for transcript

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

BP6

Variant 11-128693941-CGAGAGAGAGA-C is Benign according to our data. Variant chr11-128693941-CGAGAGAGAGA-C is described in ClinVar as [Benign]. Clinvar id is 1276147.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLI1	NM_002017.5 link	c.-317_-308delGAGAGAGAGA		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_-308delGAGAGAGAGA		upstream_gene_variant		1	NM_002017.5	ENSP00000433488.2		Q01543-1

Frequencies

GnomAD3 genomes

AF:

0.0760

AC:

6289

AN:

82696

Hom.:

206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0778

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.0917

Gnomad ASJ

AF:

0.0464

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.0992

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.0286

Gnomad NFE

AF:

0.0666

Gnomad OTH

AF:

0.0630

GnomAD4 exome

AF:

0.0693

AC:

6384

AN:

92170

Hom.:

AF XY:

0.0683

AC XY:

2988

AN XY:

43768

show subpopulations

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

African (AFR)

AF:

0.0861

AC:

333

AN:

3868

American (AMR)

AF:

0.0839

AC:

226

AN:

2694

Ashkenazi Jewish (ASJ)

AF:

0.0439

AC:

232

AN:

5282

East Asian (EAS)

AF:

0.129

AC:

1462

AN:

11332

South Asian (SAS)

AF:

0.0507

AC:

AN:

1756

European-Finnish (FIN)

AF:

0.0996

AC:

197

AN:

1978

Middle Eastern (MID)

AF:

0.0652

AC:

AN:

552

European-Non Finnish (NFE)

AF:

0.0581

AC:

3339

AN:

57430

Other (OTH)

AF:

0.0646

AC:

470

AN:

7278

⚠️ 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: 0.335

Heterozygous variant carriers

386

772

1158

1544

1930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0760

AC:

6289

AN:

82720

Hom.:

205

Cov.:

AF XY:

0.0795

AC XY:

3032

AN XY:

38128

show subpopulations

African (AFR)

AF:

0.0779

AC:

1434

AN:

18408

American (AMR)

AF:

0.0917

AC:

717

AN:

7818

Ashkenazi Jewish (ASJ)

AF:

0.0464

AC:

115

AN:

2476

East Asian (EAS)

AF:

0.125

AC:

337

AN:

2700

South Asian (SAS)

AF:

0.0980

AC:

207

AN:

2112

European-Finnish (FIN)

AF:

0.120

AC:

380

AN:

3176

Middle Eastern (MID)

AF:

0.0299

AC:

AN:

134

European-Non Finnish (NFE)

AF:

0.0666

AC:

2943

AN:

44162

Other (OTH)

AF:

0.0640

AC:

AN:

1172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

241

482

724

965

1206

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 18, 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

=296/4

polymorphism (auto)

(source)

Splicing

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

Publications

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11-128693941-CGAGAGAGAGA-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