chr11-128693941-C-CGAGAGAGA

Variant names:

• chr11-128693941-C-CGAGAGAGA
• rs57930585
• ENST00000526269.2:n.112-558_112-551dupTCTCTCTC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001440369.1(FLI1):​c.-82+843_-82+850dupGAGAGAGA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0047 (15 hom., cov: 0)
  • Exomes 𝑓: 0.0027 (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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00475 (393/82814) while in subpopulation AFR AF = 0.00619 (114/18420). AF 95% confidence interval is 0.00527. There are 15 homozygotes in GnomAd4. There are 171 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 AD,AR gene

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+843_-82+850dupGAGAGAGA		intron	N/A	NP_001427298.1
	FLI1	NM_001440370.1		c.-82+8614_-82+8621dupGAGAGAGA		intron	N/A	NP_001427299.1
	FLI1	NM_001440371.1		c.-82+1186_-82+1193dupGAGAGAGA		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.112-558_112-551dupTCTCTCTC		intron	N/A
	FLI1	ENST00000897157.1		c.-273_-266dupGAGAGAGA		5_prime_UTR	Exon 1 of 10	ENSP00000567216.1
	FLI1	ENST00000897156.1		c.-273_-266dupGAGAGAGA		5_prime_UTR	Exon 1 of 8	ENSP00000567215.1

Frequencies

GnomAD3 genomes AF: 0.00475 AC: 393 AN: 82790 Hom.: 15 Cov.: 0

Gnomad AFR AF: 0.00621

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00230

Gnomad ASJ AF: 0.000403

Gnomad EAS AF: 0.00295

Gnomad SAS AF: 0.00329

Gnomad FIN AF: 0.00220

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00534

Gnomad OTH AF: 0.00173

GnomAD4 exome AF: 0.00267 AC: 250 AN: 93544 Hom.: 0 Cov.: 0 AF XY: 0.00236 AC XY: 105 AN XY: 44432

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

African (AFR) AF: 0.00408 AC: 16 AN: 3926

American (AMR) AF: 0.00219 AC: 6 AN: 2744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5364

East Asian (EAS) AF: 0.00199 AC: 23 AN: 11574

South Asian (SAS) AF: 0.000564 AC: 1 AN: 1774

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

Middle Eastern (MID) AF: 0.00350 AC: 2 AN: 572

European-Non Finnish (NFE) AF: 0.00315 AC: 183 AN: 58176

Other (OTH) AF: 0.00256 AC: 19 AN: 7416

⚠️ 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: 0.00475 AC: 393 AN: 82814 Hom.: 15 Cov.: 0 AF XY: 0.00448 AC XY: 171 AN XY: 38162

African (AFR) AF: 0.00619 AC: 114 AN: 18420

American (AMR) AF: 0.00230 AC: 18 AN: 7830

Ashkenazi Jewish (ASJ) AF: 0.000403 AC: 1 AN: 2484

East Asian (EAS) AF: 0.00296 AC: 8 AN: 2702

South Asian (SAS) AF: 0.00331 AC: 7 AN: 2114

European-Finnish (FIN) AF: 0.00220 AC: 7 AN: 3178

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

European-Non Finnish (NFE) AF: 0.00534 AC: 236 AN: 44214

Other (OTH) AF: 0.00171 AC: 2 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;