chr11-128693941-CGAGAGAGAGAGA-C

Variant names:

• chr11-128693941-CGAGAGAGAGAGA-C
• rs57930585
• ENST00000281428:c.-646_-635delGAGAGAGAGAGA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000281428(FLI1):​c.-646_-635delGAGAGAGAGAGA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 175,638 control chromosomes in the GnomAD database, including 39 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.022 (37 hom., cov: 0)
  • Exomes 𝑓: 0.034 (2 hom.)
• Consequence: FLI1 ENST00000281428 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85

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]

SENCR (HGNC:44177): (smooth muscle and endothelial cell enriched migration/differentiation-associated lncRNA)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLI1	NM_002017.5	c.-317_-306delGAGAGAGAGAGA		upstream_gene_variant		ENST00000527786.7	NP_002008.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLI1	ENST00000527786.7	c.-317_-306delGAGAGAGAGAGA		upstream_gene_variant		1	NM_002017.5	ENSP00000433488.2

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 1780 AN: 82798 Hom.: 37 Cov.: 0

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0595

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.00797

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.0214

Gnomad NFE AF: 0.0194

Gnomad OTH AF: 0.0181

GnomAD4 exome AF: 0.0336 AC: 3115 AN: 92816 Hom.: 2 AF XY: 0.0328 AC XY: 1445 AN XY: 44082

Gnomad4 AFR exome AF: 0.0359

Gnomad4 AMR exome AF: 0.0691

Gnomad4 ASJ exome AF: 0.0116

Gnomad4 EAS exome AF: 0.0459

Gnomad4 SAS exome AF: 0.0142

Gnomad4 FIN exome AF: 0.0464

Gnomad4 NFE exome AF: 0.0320

Gnomad4 OTH exome AF: 0.0307

GnomAD4 genome AF: 0.0215 AC: 1783 AN: 82822 Hom.: 37 Cov.: 0 AF XY: 0.0225 AC XY: 861 AN XY: 38182

Gnomad4 AFR AF: 0.0163

Gnomad4 AMR AF: 0.0601

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.0211

Gnomad4 SAS AF: 0.00756

Gnomad4 FIN AF: 0.0148

Gnomad4 NFE AF: 0.0194

Gnomad4 OTH AF: 0.0179

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs57930585; hg19: chr11-128563836;