11-128693941-CGAGAGAGAGAGAGAGAGA-C

Variant names:

• chr11-128693941-CGAGAGAGAGAGAGAGAGA-C
• rs57930585
• ENST00000281428.12:c.-652_-635delGAGAGAGAGAGAGAGAGA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000281428.12(FLI1):​c.-652_-635delGAGAGAGAGAGAGAGAGA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 176,490 control chromosomes in the GnomAD database, including 1,846 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. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (1762 hom., cov: 0)
  • Exomes 𝑓: 0.18 (84 hom.)
• Consequence: FLI1 ENST00000281428.12 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 11-128693941-CGAGAGAGAGAGAGAGAGA-C is Benign according to our data. Variant chr11-128693941-CGAGAGAGAGAGAGAGAGA-C is described in ClinVar as [Benign]. Clinvar id is 1284178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLI1	NM_002017.5	c.-317_-300delGAGAGAGAGAGAGAGAGA		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_-300delGAGAGAGAGAGAGAGAGA		upstream_gene_variant		1	NM_002017.5	ENSP00000433488.2

Frequencies

GnomAD3 genomes AF: 0.236 AC: 19605 AN: 82940 Hom.: 1759 Cov.: 0

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.181 AC: 16893 AN: 93526 Hom.: 84 AF XY: 0.184 AC XY: 8170 AN XY: 44408

African (AFR) AF: 0.106 AC: 416 AN: 3920

American (AMR) AF: 0.123 AC: 338 AN: 2742

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 1226 AN: 5344

East Asian (EAS) AF: 0.124 AC: 1437 AN: 11570

South Asian (SAS) AF: 0.0705 AC: 125 AN: 1772

European-Finnish (FIN) AF: 0.209 AC: 415 AN: 1990

Middle Eastern (MID) AF: 0.229 AC: 131 AN: 572

European-Non Finnish (NFE) AF: 0.197 AC: 11443 AN: 58226

Other (OTH) AF: 0.184 AC: 1362 AN: 7390

GnomAD4 genome AF: 0.236 AC: 19609 AN: 82964 Hom.: 1762 Cov.: 0 AF XY: 0.236 AC XY: 9030 AN XY: 38260

African (AFR) AF: 0.156 AC: 2882 AN: 18444

American (AMR) AF: 0.218 AC: 1709 AN: 7852

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 848 AN: 2484

East Asian (EAS) AF: 0.238 AC: 644 AN: 2704

South Asian (SAS) AF: 0.206 AC: 437 AN: 2118

European-Finnish (FIN) AF: 0.235 AC: 749 AN: 3194

Middle Eastern (MID) AF: 0.410 AC: 55 AN: 134

European-Non Finnish (NFE) AF: 0.267 AC: 11835 AN: 44292

Other (OTH) AF: 0.270 AC: 316 AN: 1170

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9
Mutation Taster		=90/10	polymorphism (auto)

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;