Genetic Variant NM_002017.5:c.*1577C>A (chr11-128812565-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002017.5(FLI1):c.*1577C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 223,138 control chromosomes in the GnomAD database, including 8,420 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5304 hom., cov: 33)

Exomes 𝑓: 0.29 ( 3116 hom. )

Consequence

FLI1
NM_002017.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.263

Publications

5 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 Gene-Disease associations (from GenCC):

bleeding disorder, platelet-type, 21
Inheritance: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

FLI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002017.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLI1	NM_002017.5	MANE Select	c.*1577C>A	3_prime_UTR	Exon 9 of 9	NP_002008.2
FLI1	NM_001167681.3		c.*1577C>A	3_prime_UTR	Exon 10 of 10	NP_001161153.1	Q01543-3
FLI1	NM_001440369.1		c.*1577C>A	3_prime_UTR	Exon 9 of 9	NP_001427298.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLI1	ENST00000527786.7	TSL:1 MANE Select	c.*1577C>A	3_prime_UTR	Exon 9 of 9	ENSP00000433488.2	Q01543-1
FLI1	ENST00000534087.3	TSL:2	c.*1577C>A	3_prime_UTR	Exon 10 of 10	ENSP00000432950.1	Q01543-3
FLI1	ENST00000429175.7	TSL:1	n.*2858C>A	downstream_gene	N/A	ENSP00000399985.3	A0A0A0MSR4

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38245

AN:

151958

Hom.:

5300

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.398

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.252

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.191

Gnomad NFE

AF:

0.324

Gnomad OTH

AF:

0.251

GnomAD4 exome

AF:

0.291

AC:

20650

AN:

71062

Hom.:

3116

Cov.:

AF XY:

0.291

AC XY:

9537

AN XY:

32784

show subpopulations

African (AFR)

AF:

0.112

AC:

382

AN:

3426

American (AMR)

AF:

0.211

AC:

448

AN:

2122

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

959

AN:

4502

East Asian (EAS)

AF:

0.337

AC:

3439

AN:

10194

South Asian (SAS)

AF:

0.217

AC:

139

AN:

640

European-Finnish (FIN)

AF:

0.205

AC:

AN:

Middle Eastern (MID)

AF:

0.260

AC:

116

AN:

446

European-Non Finnish (NFE)

AF:

0.311

AC:

13609

AN:

43754

Other (OTH)

AF:

0.261

AC:

1549

AN:

5934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

687

1374

2061

2748

3435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.252

AC:

38262

AN:

152076

Hom.:

5304

Cov.:

AF XY:

0.251

AC XY:

18663

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.126

AC:

5235

AN:

41498

American (AMR)

AF:

0.220

AC:

3359

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

709

AN:

3464

East Asian (EAS)

AF:

0.253

AC:

1305

AN:

5168

South Asian (SAS)

AF:

0.233

AC:

1121

AN:

4812

European-Finnish (FIN)

AF:

0.337

AC:

3555

AN:

10552

Middle Eastern (MID)

AF:

0.182

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.324

AC:

22030

AN:

67978

Other (OTH)

AF:

0.252

AC:

533

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1457

2915

4372

5830

7287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.290

Hom.:

902

Bravo

AF:

0.237

Asia WGS

AF:

0.228

AC:

793

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.6

(source)

DANN

Benign

0.68

PhyloP100

0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over