rs654723

Variant names:

• chr11-128716260-C-A
• rs654723
• NM_002017.5:c.18+21984C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-128716260-C-A
• chr11-128716260-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 35 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: AD, AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FLI1	NM_002017.5	c.18+21984C>A		intron_variant	Intron 1 of 8	ENST00000527786.7	NP_002008.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLI1	ENST00000527786.7	c.18+21984C>A		intron_variant	Intron 1 of 8	1	NM_002017.5	ENSP00000433488.2

Frequencies

GnomAD3 genomes AF: 0.527 AC: 79956 AN: 151842 Hom.: 22438 Cov.: 31

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

African (AFR) AF: 0.331 AC: 13687 AN: 41404

American (AMR) AF: 0.487 AC: 7434 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1926 AN: 3470

East Asian (EAS) AF: 0.503 AC: 2593 AN: 5154

South Asian (SAS) AF: 0.707 AC: 3409 AN: 4820

European-Finnish (FIN) AF: 0.682 AC: 7211 AN: 10566

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.617 AC: 41897 AN: 67950

Other (OTH) AF: 0.531 AC: 1121 AN: 2112

Alfa AF: 0.578 Hom.: 109679

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
PhyloP100		1.0
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: rs654723; hg19: chr11-128586155;