11-128693941-CGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA-CGAGAGAGAGAGAGAGA

Variant names:

• chr11-128693941-CGAGAGAGAGAGAGAGAGAGAGA-C
• rs57930585
• ENST00000281428.12:c.-656_-635delGAGAGAGAGAGAGAGAGAGAGA

Variant summary

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

The ENST00000281428.12(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. 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 0.0080 (1 hom., cov: 0)
  • Exomes 𝑓: 0.014 (3 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 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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• 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

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

African (AFR) AF: 0.00559 AC: 22 AN: 3936

American (AMR) AF: 0.0160 AC: 44 AN: 2744

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 63 AN: 5320

East Asian (EAS) AF: 0.00449 AC: 52 AN: 11584

South Asian (SAS) AF: 0.0130 AC: 23 AN: 1770

European-Finnish (FIN) AF: 0.0221 AC: 44 AN: 1990

Middle Eastern (MID) AF: 0.00523 AC: 3 AN: 574

European-Non Finnish (NFE) AF: 0.0169 AC: 983 AN: 58168

Other (OTH) AF: 0.0135 AC: 100 AN: 7394

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

African (AFR) AF: 0.00494 AC: 91 AN: 18424

American (AMR) AF: 0.0137 AC: 107 AN: 7832

Ashkenazi Jewish (ASJ) AF: 0.00684 AC: 17 AN: 2484

East Asian (EAS) AF: 0.00185 AC: 5 AN: 2704

South Asian (SAS) AF: 0.00142 AC: 3 AN: 2116

European-Finnish (FIN) AF: 0.00283 AC: 9 AN: 3180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 134

European-Non Finnish (NFE) AF: 0.00898 AC: 397 AN: 44204

Other (OTH) AF: 0.0119 AC: 14 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;