11-128693941-CGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA-CGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA

Variant names:

• chr11-128693941-C-CGAGA
• rs57930585
• ENST00000281428.12:c.-638_-635dupGAGA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000281428.12(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 ENST00000281428.12 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.709
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0110 AC: 43 AN: 3902

American (AMR) AF: 0.00884 AC: 24 AN: 2714

Ashkenazi Jewish (ASJ) AF: 0.00943 AC: 50 AN: 5300

East Asian (EAS) AF: 0.0148 AC: 169 AN: 11404

South Asian (SAS) AF: 0.00623 AC: 11 AN: 1766

European-Finnish (FIN) AF: 0.000501 AC: 1 AN: 1998

Middle Eastern (MID) AF: 0.0124 AC: 7 AN: 566

European-Non Finnish (NFE) AF: 0.00983 AC: 566 AN: 57576

Other (OTH) AF: 0.0100 AC: 73 AN: 7280

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.0186 AC: 343 AN: 18420

American (AMR) AF: 0.0224 AC: 175 AN: 7804

Ashkenazi Jewish (ASJ) AF: 0.0177 AC: 44 AN: 2480

East Asian (EAS) AF: 0.0186 AC: 50 AN: 2692

South Asian (SAS) AF: 0.00901 AC: 19 AN: 2108

European-Finnish (FIN) AF: 0.0120 AC: 38 AN: 3178

Middle Eastern (MID) AF: 0.0149 AC: 2 AN: 134

European-Non Finnish (NFE) AF: 0.0195 AC: 863 AN: 44172

Other (OTH) AF: 0.0154 AC: 18 AN: 1168

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs57930585; hg19: chr11-128563836;