ENST00000281428:c.-640_-635dupGAGAGA

Variant names:

• chr11-128693941-C-CGAGAGA
• rs57930585
• ENST00000281428:c.-640_-635dupGAGAGA

Variant summary

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

The ENST00000281428(FLI1):​c.-640_-635dupGAGAGA 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 0.0082 (21 hom., cov: 0)
  • Exomes 𝑓: 0.0060 (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 eas. gnomad4 allele frequency = 0.00823 (681/82792) while in subpopulation EAS AF= 0.01 (27/2698). AF 95% confidence interval is 0.00801. There are 21 homozygotes in gnomad4. There are 303 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 AD,AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00822 AC: 680 AN: 82770 Hom.: 21 Cov.: 0

Gnomad AFR AF: 0.00882

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00818

Gnomad ASJ AF: 0.00282

Gnomad EAS AF: 0.00996

Gnomad SAS AF: 0.00610

Gnomad FIN AF: 0.00409

Gnomad MID AF: 0.00725

Gnomad NFE AF: 0.00873

Gnomad OTH AF: 0.00604

GnomAD4 exome AF: 0.00596 AC: 555 AN: 93160 Hom.: 0 Cov.: 0 AF XY: 0.00572 AC XY: 253 AN XY: 44236

Gnomad4 AFR exome AF: 0.00718

Gnomad4 AMR exome AF: 0.00366

Gnomad4 ASJ exome AF: 0.00187

Gnomad4 EAS exome AF: 0.0103

Gnomad4 SAS exome AF: 0.00508

Gnomad4 FIN exome AF: 0.000501

Gnomad4 NFE exome AF: 0.00562

Gnomad4 OTH exome AF: 0.00599

GnomAD4 genome AF: 0.00823 AC: 681 AN: 82792 Hom.: 21 Cov.: 0 AF XY: 0.00794 AC XY: 303 AN XY: 38148

Gnomad4 AFR AF: 0.00890

Gnomad4 AMR AF: 0.00818

Gnomad4 ASJ AF: 0.00282

Gnomad4 EAS AF: 0.0100

Gnomad4 SAS AF: 0.00568

Gnomad4 FIN AF: 0.00409

Gnomad4 NFE AF: 0.00873

Gnomad4 OTH AF: 0.00597

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;