rs531894

Positions:

• chr11-128758861-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.230+535T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,984 control chromosomes in the GnomAD database, including 14,525 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 0.43 (14525 hom., cov: 31)
• Consequence: FLI1 NM_002017.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.922

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLI1	NM_002017.5	c.230+535T>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.230+535T>C		intron_variant		1	NM_002017.5	ENSP00000433488	P1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65817 AN: 151866 Hom.: 14532 Cov.: 31

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.433 AC: 65838 AN: 151984 Hom.: 14525 Cov.: 31 AF XY: 0.438 AC XY: 32539 AN XY: 74246

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.425

Alfa AF: 0.436 Hom.: 2056

Bravo AF: 0.424

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	-0.87
CADD	Benign	0.83
DANN	Benign	0.36

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: rs531894; hg19: chr11-128628756;