rs496844

Positions:

• chr11-128780134-C-G
• chr11-128780134-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.590-1824C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,074 control chromosomes in the GnomAD database, including 13,605 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 0.41 (13605 hom., cov: 33)
• Consequence: FLI1 NM_002017.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLI1	NM_002017.5	c.590-1824C>G		intron_variant		ENST00000527786.7	NP_002008.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLI1	ENST00000527786.7	c.590-1824C>G		intron_variant		1	NM_002017.5	ENSP00000433488.2

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61623 AN: 151956 Hom.: 13591 Cov.: 33

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.405 AC: 61665 AN: 152074 Hom.: 13605 Cov.: 33 AF XY: 0.403 AC XY: 29975 AN XY: 74336

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.485

Alfa AF: 0.425 Hom.: 1815

Bravo AF: 0.408

Asia WGS AF: 0.345 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.9
DANN	Benign	0.71

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: rs496844; hg19: chr11-128650029;