rs665440

Positions:

• chr11-128712662-T-C

Variant summary

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

The NM_002017.5(FLI1):​c.18+18386T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 152,146 control chromosomes in the GnomAD database, including 343 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 0.063 (343 hom., cov: 32)
• Consequence: FLI1 NM_002017.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLI1	NM_002017.5	c.18+18386T>C		intron_variant		ENST00000527786.7	NP_002008.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLI1	ENST00000527786.7	c.18+18386T>C		intron_variant		1	NM_002017.5	ENSP00000433488	P1

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9593 AN: 152028 Hom.: 342 Cov.: 32

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0671

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.0411

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0620

Gnomad OTH AF: 0.0805

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

GnomAD4 genome AF: 0.0631 AC: 9601 AN: 152146 Hom.: 343 Cov.: 32 AF XY: 0.0600 AC XY: 4463 AN XY: 74396

Gnomad4 AFR AF: 0.0786

Gnomad4 AMR AF: 0.0670

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00622

Gnomad4 FIN AF: 0.0411

Gnomad4 NFE AF: 0.0620

Gnomad4 OTH AF: 0.0801

Alfa AF: 0.0630 Hom.: 91

Bravo AF: 0.0657

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.58

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: rs665440; hg19: chr11-128582557;