chr11-128693941-CGAGAGAGAGAGA-C

Variant names:

• chr11-128693941-CGAGAGAGAGAGA-C
• rs57930585
• ENST00000526269.2:n.112-562_112-551delTCTCTCTCTCTC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001440369.1(FLI1):​c.-82+839_-82+850delGAGAGAGAGAGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 175,638 control chromosomes in the GnomAD database, including 39 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 0.022 (37 hom., cov: 0)
  • Exomes 𝑓: 0.034 (2 hom.)
• Consequence: FLI1 NM_001440369.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85
• Publications: 0 publications found

Genes affected

SENCR (HGNC:44177): (smooth muscle and endothelial cell enriched migration/differentiation-associated lncRNA)

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]

FLI1 Gene-Disease associations (from GenCC):

• bleeding disorder, platelet-type, 21

  Inheritance: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0556 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001440369.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLI1	NM_001440369.1		c.-82+839_-82+850delGAGAGAGAGAGA		intron	N/A	NP_001427298.1
	FLI1	NM_001440370.1		c.-82+8610_-82+8621delGAGAGAGAGAGA		intron	N/A	NP_001427299.1
	FLI1	NM_001440371.1		c.-82+1182_-82+1193delGAGAGAGAGAGA		intron	N/A	NP_001427300.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SENCR	ENST00000526269.2	TSL:1	n.112-562_112-551delTCTCTCTCTCTC		intron	N/A
	FLI1	ENST00000897157.1		c.-277_-266delGAGAGAGAGAGA		5_prime_UTR	Exon 1 of 10	ENSP00000567216.1
	FLI1	ENST00000897156.1		c.-277_-266delGAGAGAGAGAGA		5_prime_UTR	Exon 1 of 8	ENSP00000567215.1

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 1780 AN: 82798 Hom.: 37 Cov.: 0

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0595

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.00797

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.0214

Gnomad NFE AF: 0.0194

Gnomad OTH AF: 0.0181

GnomAD4 exome AF: 0.0336 AC: 3115 AN: 92816 Hom.: 2 AF XY: 0.0328 AC XY: 1445 AN XY: 44082

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

African (AFR) AF: 0.0359 AC: 140 AN: 3896

American (AMR) AF: 0.0691 AC: 186 AN: 2690

Ashkenazi Jewish (ASJ) AF: 0.0116 AC: 62 AN: 5328

East Asian (EAS) AF: 0.0459 AC: 523 AN: 11402

South Asian (SAS) AF: 0.0142 AC: 25 AN: 1764

European-Finnish (FIN) AF: 0.0464 AC: 92 AN: 1982

Middle Eastern (MID) AF: 0.0194 AC: 11 AN: 566

European-Non Finnish (NFE) AF: 0.0320 AC: 1851 AN: 57852

Other (OTH) AF: 0.0307 AC: 225 AN: 7336

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0215 AC: 1783 AN: 82822 Hom.: 37 Cov.: 0 AF XY: 0.0225 AC XY: 861 AN XY: 38182

African (AFR) AF: 0.0163 AC: 301 AN: 18428

American (AMR) AF: 0.0601 AC: 470 AN: 7822

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 10 AN: 2484

East Asian (EAS) AF: 0.0211 AC: 57 AN: 2702

South Asian (SAS) AF: 0.00756 AC: 16 AN: 2116

European-Finnish (FIN) AF: 0.0148 AC: 47 AN: 3184

Middle Eastern (MID) AF: 0.0224 AC: 3 AN: 134

European-Non Finnish (NFE) AF: 0.0194 AC: 858 AN: 44212

Other (OTH) AF: 0.0179 AC: 21 AN: 1174

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9
Mutation Taster		=299/1	polymorphism

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;