chr11-128693941-C-CGAGAGAGAGAGAGAGA

Variant names:

• chr11-128693941-C-CGAGAGAGAGAGAGAGA
• rs57930585
• ENST00000526269.2:n.112-566_112-551dupTCTCTCTCTCTCTCTC

Variant summary

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

The NM_001440369.1(FLI1):​c.-82+835_-82+850dupGAGAGAGAGAGAGAGA 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 0.000085 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000043 (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 amr. GnomAd4 allele frequency = 0.0000845 (7/82836) while in subpopulation AMR AF = 0.000128 (1/7832). AF 95% confidence interval is 0.000044. There are 0 homozygotes in GnomAd4. There are 2 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+835_-82+850dupGAGAGAGAGAGAGAGA		intron	N/A	NP_001427298.1
	FLI1	NM_001440370.1		c.-82+8606_-82+8621dupGAGAGAGAGAGAGAGA		intron	N/A	NP_001427299.1
	FLI1	NM_001440371.1		c.-82+1178_-82+1193dupGAGAGAGAGAGAGAGA		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.112-566_112-551dupTCTCTCTCTCTCTCTC		intron	N/A
	FLI1	ENST00000897157.1		c.-281_-266dupGAGAGAGAGAGAGAGA		5_prime_UTR	Exon 1 of 10	ENSP00000567216.1
	FLI1	ENST00000897156.1		c.-281_-266dupGAGAGAGAGAGAGAGA		5_prime_UTR	Exon 1 of 8	ENSP00000567215.1

Frequencies

GnomAD3 genomes AF: 0.0000845 AC: 7 AN: 82812 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000544

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: 0.000113

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000426 AC: 4 AN: 93896 Hom.: 0 Cov.: 0 AF XY: 0.0000224 AC XY: 1 AN XY: 44572

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

African (AFR) AF: 0.00 AC: 0 AN: 3944

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: 0.0000684 AC: 4 AN: 58452

Other (OTH) AF: 0.00 AC: 0 AN: 7422

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000135934), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000845 AC: 7 AN: 82836 Hom.: 0 Cov.: 0 AF XY: 0.0000524 AC XY: 2 AN XY: 38180

African (AFR) AF: 0.0000543 AC: 1 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: 0.000113 AC: 5 AN: 44220

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

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;