11-128693941-CGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA-CGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001440369.1(FLI1):​c.-82+843_-82+850delGAGAGAGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0545 in 174,414 control chromosomes in the GnomAD database, including 103 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (101 hom., cov: 0)
  • Exomes 𝑓: 0.067 (2 hom.)
• Consequence: FLI1 NM_001440369.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.53
• 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 -10 ACMG points.

• BP6: Variant 11-128693941-CGAGAGAGA-C is Benign according to our data. Variant chr11-128693941-CGAGAGAGA-C is described in ClinVar as Benign. ClinVar VariationId is 1232949.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0861 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+843_-82+850delGAGAGAGA		intron	N/A	NP_001427298.1
	FLI1	NM_001440370.1		c.-82+8614_-82+8621delGAGAGAGA		intron	N/A	NP_001427299.1
	FLI1	NM_001440371.1		c.-82+1186_-82+1193delGAGAGAGA		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_112-551delTCTCTCTC		intron	N/A
	FLI1	ENST00000897157.1		c.-273_-266delGAGAGAGA		5_prime_UTR	Exon 1 of 10	ENSP00000567216.1
	FLI1	ENST00000897156.1		c.-273_-266delGAGAGAGA		5_prime_UTR	Exon 1 of 8	ENSP00000567215.1

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 3385 AN: 82750 Hom.: 101 Cov.: 0

Gnomad AFR AF: 0.0899

Gnomad AMI AF: 0.00177

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0246

Gnomad EAS AF: 0.0772

Gnomad SAS AF: 0.0371

Gnomad FIN AF: 0.0611

Gnomad MID AF: 0.00714

Gnomad NFE AF: 0.0202

Gnomad OTH AF: 0.0363

GnomAD4 exome AF: 0.0667 AC: 6116 AN: 91640 Hom.: 2 AF XY: 0.0639 AC XY: 2780 AN XY: 43534

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

African (AFR) AF: 0.110 AC: 422 AN: 3822

American (AMR) AF: 0.0664 AC: 179 AN: 2694

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 287 AN: 5220

East Asian (EAS) AF: 0.101 AC: 1132 AN: 11262

South Asian (SAS) AF: 0.0428 AC: 75 AN: 1754

European-Finnish (FIN) AF: 0.0785 AC: 154 AN: 1962

Middle Eastern (MID) AF: 0.0461 AC: 26 AN: 564

European-Non Finnish (NFE) AF: 0.0591 AC: 3378 AN: 57116

Other (OTH) AF: 0.0639 AC: 463 AN: 7246

⚠️ 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: 0.0409 AC: 3385 AN: 82774 Hom.: 101 Cov.: 0 AF XY: 0.0428 AC XY: 1635 AN XY: 38162

African (AFR) AF: 0.0897 AC: 1651 AN: 18410

American (AMR) AF: 0.0323 AC: 253 AN: 7830

Ashkenazi Jewish (ASJ) AF: 0.0246 AC: 61 AN: 2484

East Asian (EAS) AF: 0.0772 AC: 208 AN: 2694

South Asian (SAS) AF: 0.0369 AC: 78 AN: 2116

European-Finnish (FIN) AF: 0.0611 AC: 194 AN: 3176

Middle Eastern (MID) AF: 0.00746 AC: 1 AN: 134

European-Non Finnish (NFE) AF: 0.0203 AC: 895 AN: 44196

Other (OTH) AF: 0.0368 AC: 43 AN: 1170

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=298/2	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;