ENST00000281428:c.-642_-635dupGAGAGAGA

Variant names:

• chr11-128693941-C-CGAGAGAGA
• rs57930585
• ENST00000281428:c.-642_-635dupGAGAGAGA

Variant summary

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

The ENST00000281428(FLI1):​c.-642_-635dupGAGAGAGA 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 0.0047 (15 hom., cov: 0)
  • Exomes 𝑓: 0.0027 (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 afr. gnomad4 allele frequency = 0.00475 (393/82814) while in subpopulation AFR AF= 0.00619 (114/18420). AF 95% confidence interval is 0.00527. There are 15 homozygotes in gnomad4. There are 171 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AD,AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00475 AC: 393 AN: 82790 Hom.: 15 Cov.: 0

Gnomad AFR AF: 0.00621

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00230

Gnomad ASJ AF: 0.000403

Gnomad EAS AF: 0.00295

Gnomad SAS AF: 0.00329

Gnomad FIN AF: 0.00220

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00534

Gnomad OTH AF: 0.00173

GnomAD4 exome AF: 0.00267 AC: 250 AN: 93544 Hom.: 0 Cov.: 0 AF XY: 0.00236 AC XY: 105 AN XY: 44432

Gnomad4 AFR exome AF: 0.00408

Gnomad4 AMR exome AF: 0.00219

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00199

Gnomad4 SAS exome AF: 0.000564

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00315

Gnomad4 OTH exome AF: 0.00256

GnomAD4 genome AF: 0.00475 AC: 393 AN: 82814 Hom.: 15 Cov.: 0 AF XY: 0.00448 AC XY: 171 AN XY: 38162

Gnomad4 AFR AF: 0.00619

Gnomad4 AMR AF: 0.00230

Gnomad4 ASJ AF: 0.000403

Gnomad4 EAS AF: 0.00296

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.00220

Gnomad4 NFE AF: 0.00534

Gnomad4 OTH AF: 0.00171

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;