11-128693941-CGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA-CGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA

Variant names:

• chr11-128693941-C-CGAGAGAGAGAGAGA
• rs57930585
• ENST00000281428.12:c.-648_-635dupGAGAGAGAGAGAGA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The ENST00000281428.12(FLI1):​c.-648_-635dupGAGAGAGAGAGAGA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_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 0.00017 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00019 (0 hom.)
• 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000169 (14/82836) while in subpopulation AFR AF = 0.000217 (4/18426). AF 95% confidence interval is 0.000105. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000169 AC: 14 AN: 82812 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000128

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000203

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000192 AC: 18 AN: 93856 Hom.: 0 Cov.: 0 AF XY: 0.000157 AC XY: 7 AN XY: 44566

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

African (AFR) AF: 0.000254 AC: 1 AN: 3940

American (AMR) AF: 0.000363 AC: 1 AN: 2752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5370

East Asian (EAS) AF: 0.00 AC: 0 AN: 11604

South Asian (SAS) AF: 0.00 AC: 0 AN: 1776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 574

European-Non Finnish (NFE) AF: 0.000240 AC: 14 AN: 58420

Other (OTH) AF: 0.000269 AC: 2 AN: 7422

⚠️ 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: 0.000169 AC: 14 AN: 82836 Hom.: 0 Cov.: 0 AF XY: 0.000105 AC XY: 4 AN XY: 38180

African (AFR) AF: 0.000217 AC: 4 AN: 18426

American (AMR) AF: 0.000128 AC: 1 AN: 7832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2484

East Asian (EAS) AF: 0.00 AC: 0 AN: 2702

South Asian (SAS) AF: 0.00 AC: 0 AN: 2116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3184

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

European-Non Finnish (NFE) AF: 0.000204 AC: 9 AN: 44220

Other (OTH) AF: 0.00 AC: 0 AN: 1172

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;