11-128759040-C-T

Position:

• chr11-128759040-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.230+714C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,096 control chromosomes in the GnomAD database, including 15,571 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 0.45 (15571 hom., cov: 33)
• Consequence: FLI1 NM_002017.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.72

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLI1	NM_002017.5	c.230+714C>T		intron_variant		ENST00000527786.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLI1	ENST00000527786.7	c.230+714C>T		intron_variant		1	NM_002017.5	P1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68141 AN: 151980 Hom.: 15574 Cov.: 33

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.448 AC: 68175 AN: 152096 Hom.: 15571 Cov.: 33 AF XY: 0.453 AC XY: 33642 AN XY: 74346

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.441

Alfa AF: 0.428 Hom.: 8271

Bravo AF: 0.442

Asia WGS AF: 0.552 AC: 1920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.048
DANN	Benign	0.63

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: rs631647; hg19: chr11-128628935;