ENST00000281428:c.-636_-635dupGA

Variant names:

• chr11-128693941-C-CGA
• rs57930585
• ENST00000281428:c.-636_-635dupGA

Variant summary

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

The ENST00000281428(FLI1):​c.-636_-635dupGA 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 0.024 (94 hom., cov: 0)
  • Exomes 𝑓: 0.016 (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 = 0.0243 (2008/82708) while in subpopulation EAS AF= 0.0342 (92/2694). AF 95% confidence interval is 0.0285. There are 94 homozygotes in gnomad4. There are 919 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 94 AD,AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0243 AC: 2009 AN: 82684 Hom.: 94 Cov.: 0

Gnomad AFR AF: 0.0292

Gnomad AMI AF: 0.0372

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.0351

Gnomad SAS AF: 0.0198

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.0143

Gnomad NFE AF: 0.0230

Gnomad OTH AF: 0.0242

GnomAD4 exome AF: 0.0165 AC: 1515 AN: 91988 Hom.: 0 Cov.: 0 AF XY: 0.0164 AC XY: 716 AN XY: 43694

Gnomad4 AFR exome AF: 0.0211

Gnomad4 AMR exome AF: 0.0137

Gnomad4 ASJ exome AF: 0.0257

Gnomad4 EAS exome AF: 0.0262

Gnomad4 SAS exome AF: 0.0119

Gnomad4 FIN exome AF: 0.00301

Gnomad4 NFE exome AF: 0.0144

Gnomad4 OTH exome AF: 0.0144

GnomAD4 genome AF: 0.0243 AC: 2008 AN: 82708 Hom.: 94 Cov.: 0 AF XY: 0.0241 AC XY: 919 AN XY: 38102

Gnomad4 AFR AF: 0.0292

Gnomad4 AMR AF: 0.0174

Gnomad4 ASJ AF: 0.0383

Gnomad4 EAS AF: 0.0341

Gnomad4 SAS AF: 0.0194

Gnomad4 FIN AF: 0.0119

Gnomad4 NFE AF: 0.0230

Gnomad4 OTH AF: 0.0239

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;