ENST00000281428:c.-656_-635delGAGAGAGAGAGAGAGAGAGAGA

Variant names:

• chr11-128693941-CGAGAGAGAGAGAGAGAGAGAGA-C
• rs57930585
• ENST00000281428:c.-656_-635delGAGAGAGAGAGAGAGAGAGAGA

Variant summary

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

The ENST00000281428(FLI1):​c.-656_-635delGAGAGAGAGAGAGAGAGAGAGA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 176,296 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0080 (1 hom., cov: 0)
  • Exomes 𝑓: 0.014 (3 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.

• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00798 (661/82816) while in subpopulation AMR AF= 0.0137 (107/7832). AF 95% confidence interval is 0.0116. There are 1 homozygotes in gnomad4. There are 312 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLI1	NM_002017.5	c.-317_-296delGAGAGAGAGAGAGAGAGAGAGA		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_-296delGAGAGAGAGAGAGAGAGAGAGA		upstream_gene_variant		1	NM_002017.5	ENSP00000433488.2

Frequencies

GnomAD3 genomes AF: 0.00797 AC: 660 AN: 82792 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00495

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.00684

Gnomad EAS AF: 0.00184

Gnomad SAS AF: 0.00141

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00898

Gnomad OTH AF: 0.0121

GnomAD4 exome AF: 0.0143 AC: 1334 AN: 93480 Hom.: 3 AF XY: 0.0154 AC XY: 683 AN XY: 44360

Gnomad4 AFR exome AF: 0.00559

Gnomad4 AMR exome AF: 0.0160

Gnomad4 ASJ exome AF: 0.0118

Gnomad4 EAS exome AF: 0.00449

Gnomad4 SAS exome AF: 0.0130

Gnomad4 FIN exome AF: 0.0221

Gnomad4 NFE exome AF: 0.0169

Gnomad4 OTH exome AF: 0.0135

GnomAD4 genome AF: 0.00798 AC: 661 AN: 82816 Hom.: 1 Cov.: 0 AF XY: 0.00817 AC XY: 312 AN XY: 38172

Gnomad4 AFR AF: 0.00494

Gnomad4 AMR AF: 0.0137

Gnomad4 ASJ AF: 0.00684

Gnomad4 EAS AF: 0.00185

Gnomad4 SAS AF: 0.00142

Gnomad4 FIN AF: 0.00283

Gnomad4 NFE AF: 0.00898

Gnomad4 OTH AF: 0.0119

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;