rs590520

Positions:

• chr11-128750237-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002017.5(FLI1):​c.19-7878C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,066 control chromosomes in the GnomAD database, including 7,905 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 0.32 (7905 hom., cov: 32)
• Consequence: FLI1 NM_002017.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLI1	NM_002017.5	c.19-7878C>T		intron_variant		ENST00000527786.7	NP_002008.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLI1	ENST00000527786.7	c.19-7878C>T		intron_variant		1	NM_002017.5	ENSP00000433488	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47868 AN: 151946 Hom.: 7889 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.315 AC: 47932 AN: 152066 Hom.: 7905 Cov.: 32 AF XY: 0.315 AC XY: 23426 AN XY: 74358

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.316

Alfa AF: 0.294 Hom.: 10956

Bravo AF: 0.333

Asia WGS AF: 0.281 AC: 978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.80

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

Other links and lift over

dbSNP: rs590520; hg19: chr11-128620132;