ENST00000281428:c.-644_-635dupGAGAGAGAGA

Variant names:

• chr11-128693941-C-CGAGAGAGAGA
• rs57930585
• ENST00000281428:c.-644_-635dupGAGAGAGAGA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000281428(FLI1):​c.-644_-635dupGAGAGAGAGA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0013 (3 hom., cov: 0)
  • Exomes 𝑓: 0.00083 (0 hom.)
• Consequence: FLI1 ENST00000281428 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.709

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.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00134 (111/82832) while in subpopulation SAS AF= 0.00236 (5/2116). AF 95% confidence interval is 0.0014. There are 3 homozygotes in gnomad4. There are 54 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLI1	NM_002017.5	c.-318_-317insGAGAGAGAGA		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.-318_-317insGAGAGAGAGA		upstream_gene_variant		1	NM_002017.5	ENSP00000433488.2

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 112 AN: 82808 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000766

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00110

Gnomad SAS AF: 0.00281

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00714

Gnomad NFE AF: 0.00129

Gnomad OTH AF: 0.000864

GnomAD4 exome AF: 0.000831 AC: 78 AN: 93816 Hom.: 0 Cov.: 0 AF XY: 0.000651 AC XY: 29 AN XY: 44548

Gnomad4 AFR exome AF: 0.00127

Gnomad4 AMR exome AF: 0.00109

Gnomad4 ASJ exome AF: 0.000559

Gnomad4 EAS exome AF: 0.000690

Gnomad4 SAS exome AF: 0.000565

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000925

Gnomad4 OTH exome AF: 0.000540

GnomAD4 genome AF: 0.00134 AC: 111 AN: 82832 Hom.: 3 Cov.: 0 AF XY: 0.00141 AC XY: 54 AN XY: 38176

Gnomad4 AFR AF: 0.00190

Gnomad4 AMR AF: 0.000766

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00111

Gnomad4 SAS AF: 0.00236

Gnomad4 FIN AF: 0.000942

Gnomad4 NFE AF: 0.00129

Gnomad4 OTH AF: 0.000853

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;