11-128693941-CGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA-CGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA

Variant names:

• chr11-128693941-C-CGAGA
• rs57930585
• ENST00000281428:c.-638_-635dupGAGA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The ENST00000281428(FLI1):​c.-638_-635dupGAGA 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 0.019 (53 hom., cov: 0)
  • Exomes 𝑓: 0.010 (0 hom.)
  • Failed GnomAD Quality Control
• 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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0102 (944/92506) while in subpopulation EAS AF= 0.0148 (169/11404). AF 95% confidence interval is 0.013. There are 0 homozygotes in gnomad4_exome. There are 436 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 1588 AN: 82698 Hom.: 52 Cov.: 0

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.0654

Gnomad AMR AF: 0.0226

Gnomad ASJ AF: 0.0177

Gnomad EAS AF: 0.0185

Gnomad SAS AF: 0.00895

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.00714

Gnomad NFE AF: 0.0195

Gnomad OTH AF: 0.0156

GnomAD4 exome AF: 0.0102 AC: 944 AN: 92506 Hom.: 0 Cov.: 0 AF XY: 0.00992 AC XY: 436 AN XY: 43946

Gnomad4 AFR exome AF: 0.0110

Gnomad4 AMR exome AF: 0.00884

Gnomad4 ASJ exome AF: 0.00943

Gnomad4 EAS exome AF: 0.0148

Gnomad4 SAS exome AF: 0.00623

Gnomad4 FIN exome AF: 0.000501

Gnomad4 NFE exome AF: 0.00983

Gnomad4 OTH exome AF: 0.0100

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0192 AC: 1589 AN: 82722 Hom.: 53 Cov.: 0 AF XY: 0.0192 AC XY: 731 AN XY: 38120

Gnomad4 AFR AF: 0.0186

Gnomad4 AMR AF: 0.0224

Gnomad4 ASJ AF: 0.0177

Gnomad4 EAS AF: 0.0186

Gnomad4 SAS AF: 0.00901

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.0195

Gnomad4 OTH AF: 0.0154

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;