rs640098

Variant names:

• chr11-128779071-A-G
• rs640098
• NM_002017.5:c.590-2887A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002017.5(FLI1):​c.590-2887A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,186 control chromosomes in the GnomAD database, including 38,113 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 0.69 (38113 hom., cov: 33)
• Consequence: FLI1 NM_002017.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268
• Publications: 3 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.909 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLI1	NM_002017.5	MANE Select	c.590-2887A>G		intron	N/A	NP_002008.2
	FLI1	NM_001167681.3		c.491-2887A>G		intron	N/A	NP_001161153.1	Q01543-3
	FLI1	NM_001440369.1		c.491-2887A>G		intron	N/A	NP_001427298.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLI1	ENST00000527786.7	TSL:1 MANE Select	c.590-2887A>G		intron	N/A	ENSP00000433488.2	Q01543-1
	FLI1	ENST00000429175.7	TSL:1	n.*512-2887A>G		intron	N/A	ENSP00000399985.3	A0A0A0MSR4
	FLI1	ENST00000897157.1		c.590-2887A>G		intron	N/A	ENSP00000567216.1

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105181 AN: 152068 Hom.: 38053 Cov.: 33

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.699

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.692 AC: 105303 AN: 152186 Hom.: 38113 Cov.: 33 AF XY: 0.685 AC XY: 50981 AN XY: 74400

African (AFR) AF: 0.917 AC: 38110 AN: 41570

American (AMR) AF: 0.689 AC: 10553 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 2445 AN: 3472

East Asian (EAS) AF: 0.599 AC: 3098 AN: 5176

South Asian (SAS) AF: 0.541 AC: 2609 AN: 4822

European-Finnish (FIN) AF: 0.513 AC: 5417 AN: 10554

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40841 AN: 67962

Other (OTH) AF: 0.702 AC: 1485 AN: 2116

Alfa AF: 0.634 Hom.: 51884

Bravo AF: 0.718

Asia WGS AF: 0.581 AC: 2024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.72
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs640098; hg19: chr11-128648966;