11-128693941-CGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA-CGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA

Variant names:

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

Variant summary

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

The NM_001440369.1(FLI1):​c.-82+839_-82+850dupGAGAGAGAGAGA variant causes a intron 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 0.00037 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00037 (0 hom.)
• Consequence: FLI1 NM_001440369.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.709
• 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000374 (31/82830) while in subpopulation AFR AF = 0.000543 (10/18426). AF 95% confidence interval is 0.000294. There are 0 homozygotes in GnomAd4. There are 17 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

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+850dupGAGAGAGAGAGA		intron	N/A	NP_001427298.1
	FLI1	NM_001440370.1		c.-82+8610_-82+8621dupGAGAGAGAGAGA		intron	N/A	NP_001427299.1
	FLI1	NM_001440371.1		c.-82+1182_-82+1193dupGAGAGAGAGAGA		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_112-551dupTCTCTCTCTCTC		intron	N/A
	FLI1	ENST00000897157.1		c.-277_-266dupGAGAGAGAGAGA		5_prime_UTR	Exon 1 of 10	ENSP00000567216.1
	FLI1	ENST00000897156.1		c.-277_-266dupGAGAGAGAGAGA		5_prime_UTR	Exon 1 of 8	ENSP00000567215.1

Frequencies

GnomAD3 genomes AF: 0.000374 AC: 31 AN: 82806 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000544

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: 0.000430

Gnomad OTH AF: 0.000864

GnomAD4 exome AF: 0.000373 AC: 35 AN: 93832 Hom.: 0 Cov.: 0 AF XY: 0.000359 AC XY: 16 AN XY: 44550

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

African (AFR) AF: 0.000761 AC: 3 AN: 3944

American (AMR) AF: 0.00109 AC: 3 AN: 2754

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

East Asian (EAS) AF: 0.0000862 AC: 1 AN: 11600

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

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

Middle Eastern (MID) AF: 0.00174 AC: 1 AN: 574

European-Non Finnish (NFE) AF: 0.000462 AC: 27 AN: 58404

Other (OTH) AF: 0.00 AC: 0 AN: 7412

⚠️ 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: 0.000374 AC: 31 AN: 82830 Hom.: 0 Cov.: 0 AF XY: 0.000445 AC XY: 17 AN XY: 38178

African (AFR) AF: 0.000543 AC: 10 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: 2114

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: 0.000430 AC: 19 AN: 44216

Other (OTH) AF: 0.000853 AC: 1 AN: 1172

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;