dbSNP rs7130622: FLI1:c.*628A>C (chr11-128811616-A-C) – 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.*628A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 214,520 control chromosomes in the GnomAD database, including 365 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 0.038 ( 342 hom., cov: 32)

Exomes 𝑓: 0.0071 ( 23 hom. )

Consequence

FLI1
NM_002017.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.53

Publications

1 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=-0.48).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 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.*628A>C	3_prime_UTR	Exon 9 of 9	NP_002008.2
FLI1	NM_001167681.3		c.*628A>C	3_prime_UTR	Exon 10 of 10	NP_001161153.1	Q01543-3
FLI1	NM_001440369.1		c.*628A>C	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.*628A>C	3_prime_UTR	Exon 9 of 9	ENSP00000433488.2	Q01543-1
FLI1	ENST00000429175.7	TSL:1	n.*1909A>C	non_coding_transcript_exon	Exon 10 of 10	ENSP00000399985.3	A0A0A0MSR4
FLI1	ENST00000429175.7	TSL:1	n.*1909A>C	3_prime_UTR	Exon 10 of 10	ENSP00000399985.3	A0A0A0MSR4

Frequencies

GnomAD3 genomes

AF:

0.0382

AC:

5818

AN:

152148

Hom.:

340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0171

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.0263

GnomAD4 exome

AF:

0.00707

AC:

440

AN:

62254

Hom.:

Cov.:

AF XY:

0.00647

AC XY:

187

AN XY:

28894

show subpopulations

African (AFR)

AF:

0.114

AC:

308

AN:

2702

American (AMR)

AF:

0.0121

AC:

AN:

1816

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3904

East Asian (EAS)

AF:

0.00

AC:

AN:

9146

South Asian (SAS)

AF:

0.00

AC:

AN:

532

European-Finnish (FIN)

AF:

0.00

AC:

AN:

456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

376

European-Non Finnish (NFE)

AF:

0.000813

AC:

AN:

38108

Other (OTH)

AF:

0.0152

AC:

AN:

5214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0384

AC:

5840

AN:

152266

Hom.:

342

Cov.:

AF XY:

0.0374

AC XY:

2782

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.132

AC:

5468

AN:

41506

American (AMR)

AF:

0.0171

AC:

261

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000828

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000750

AC:

AN:

68032

Other (OTH)

AF:

0.0260

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

265

529

794

1058

1323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0164

Hom.:

179

Bravo

AF:

0.0436

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

3.5

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