11-128693941-CGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA-CGAGAGAGA

Variant names:

• chr11-128693941-CGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA-C
• rs57930585
• ENST00000526269.2:n.112-580_112-551delTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC

Variant summary

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

The NM_001440369.1(FLI1):​c.-82+821_-82+850delGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 176,728 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00017 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00014 (0 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000169 (14/82812) while in subpopulation NFE AF = 0.000226 (10/44228). AF 95% confidence interval is 0.000122. There are 0 homozygotes in GnomAd4. There are 8 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+821_-82+850delGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA		intron	N/A	NP_001427298.1
	FLI1	NM_001440370.1		c.-82+8592_-82+8621delGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA		intron	N/A	NP_001427299.1
	FLI1	NM_001440371.1		c.-82+1164_-82+1193delGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA		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.112-580_112-551delTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC		intron	N/A
	FLI1	ENST00000897157.1		c.-295_-266delGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA		5_prime_UTR	Exon 1 of 10	ENSP00000567216.1
	FLI1	ENST00000897156.1		c.-295_-266delGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA		5_prime_UTR	Exon 1 of 8	ENSP00000567215.1

Frequencies

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

Gnomad AFR AF: 0.000109

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: 0.000226

Gnomad OTH AF: 0.000864

GnomAD4 exome AF: 0.000138 AC: 13 AN: 93916 Hom.: 0 AF XY: 0.0000897 AC XY: 4 AN XY: 44586

African (AFR) AF: 0.000507 AC: 2 AN: 3946

American (AMR) AF: 0.00 AC: 0 AN: 2754

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 11606

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: 0.000171 AC: 10 AN: 58466

Other (OTH) AF: 0.000135 AC: 1 AN: 7426

GnomAD4 genome AF: 0.000169 AC: 14 AN: 82812 Hom.: 0 Cov.: 0 AF XY: 0.000210 AC XY: 8 AN XY: 38142

African (AFR) AF: 0.000109 AC: 2 AN: 18374

American (AMR) AF: 0.000128 AC: 1 AN: 7830

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 2716

South Asian (SAS) AF: 0.00 AC: 0 AN: 2132

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 140

European-Non Finnish (NFE) AF: 0.000226 AC: 10 AN: 44228

Other (OTH) AF: 0.000864 AC: 1 AN: 1158

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

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;