rs654723

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_002017.5(FLI1):​c.18+21984C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,960 control chromosomes in the GnomAD database, including 22,432 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 0.53 ( 22432 hom., cov: 31)

Consequence

FLI1
NM_002017.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FLI1NM_002017.5 linkuse as main transcriptc.18+21984C>A intron_variant ENST00000527786.7 NP_002008.2 Q01543-1A0A024R3M5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FLI1ENST00000527786.7 linkuse as main transcriptc.18+21984C>A intron_variant 1 NM_002017.5 ENSP00000433488.2 Q01543-1

Frequencies

GnomAD3 genomes
AF:
0.527
AC:
79956
AN:
151842
Hom.:
22438
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.331
Gnomad AMI
AF:
0.604
Gnomad AMR
AF:
0.487
Gnomad ASJ
AF:
0.555
Gnomad EAS
AF:
0.503
Gnomad SAS
AF:
0.708
Gnomad FIN
AF:
0.682
Gnomad MID
AF:
0.459
Gnomad NFE
AF:
0.617
Gnomad OTH
AF:
0.533
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.526
AC:
79963
AN:
151960
Hom.:
22432
Cov.:
31
AF XY:
0.532
AC XY:
39497
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.331
Gnomad4 AMR
AF:
0.487
Gnomad4 ASJ
AF:
0.555
Gnomad4 EAS
AF:
0.503
Gnomad4 SAS
AF:
0.707
Gnomad4 FIN
AF:
0.682
Gnomad4 NFE
AF:
0.617
Gnomad4 OTH
AF:
0.531
Alfa
AF:
0.583
Hom.:
49099
Bravo
AF:
0.497
Asia WGS
AF:
0.573
AC:
1991
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.30
CADD
Benign
16
DANN
Benign
0.82

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs654723; hg19: chr11-128586155; API