11-128693941-CGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA-CGAGAGAGAGAGAGAGAGAGAGA

Variant names:

• chr11-128693941-CGAGAGAGAGAGAGAGA-C
• rs57930585
• ENST00000281428.12:c.-650_-635delGAGAGAGAGAGAGAGA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000281428.12(FLI1):​c.-650_-635delGAGAGAGAGAGAGAGA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 176,460 control chromosomes in the GnomAD database, including 38 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.025 (36 hom., cov: 0)
  • Exomes 𝑓: 0.020 (2 hom.)
• Consequence: FLI1 ENST00000281428.12 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0252 (2089/82824) while in subpopulation AFR AF = 0.0484 (892/18420). AF 95% confidence interval is 0.0458. There are 36 homozygotes in GnomAd4. There are 969 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 36 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLI1	NM_002017.5	c.-317_-302delGAGAGAGAGAGAGAGA		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_-302delGAGAGAGAGAGAGAGA		upstream_gene_variant		1	NM_002017.5	ENSP00000433488.2

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 2083 AN: 82800 Hom.: 36 Cov.: 0

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.00177

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.00845

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.0461

Gnomad MID AF: 0.00714

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.0285

GnomAD4 exome AF: 0.0203 AC: 1904 AN: 93636 Hom.: 2 AF XY: 0.0206 AC XY: 914 AN XY: 44440

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

African (AFR) AF: 0.0303 AC: 119 AN: 3930

American (AMR) AF: 0.0219 AC: 60 AN: 2744

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 74 AN: 5362

East Asian (EAS) AF: 0.0112 AC: 130 AN: 11586

South Asian (SAS) AF: 0.0164 AC: 29 AN: 1770

European-Finnish (FIN) AF: 0.0446 AC: 89 AN: 1996

Middle Eastern (MID) AF: 0.0192 AC: 11 AN: 572

European-Non Finnish (NFE) AF: 0.0215 AC: 1251 AN: 58264

Other (OTH) AF: 0.0190 AC: 141 AN: 7412

⚠️ 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 AF: 0.0252 AC: 2089 AN: 82824 Hom.: 36 Cov.: 0 AF XY: 0.0254 AC XY: 969 AN XY: 38172

African (AFR) AF: 0.0484 AC: 892 AN: 18420

American (AMR) AF: 0.0132 AC: 103 AN: 7830

Ashkenazi Jewish (ASJ) AF: 0.00845 AC: 21 AN: 2484

East Asian (EAS) AF: 0.0156 AC: 42 AN: 2700

South Asian (SAS) AF: 0.0161 AC: 34 AN: 2116

European-Finnish (FIN) AF: 0.0461 AC: 147 AN: 3188

Middle Eastern (MID) AF: 0.00746 AC: 1 AN: 134

European-Non Finnish (NFE) AF: 0.0184 AC: 815 AN: 44214

Other (OTH) AF: 0.0282 AC: 33 AN: 1172

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9

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;