11-128693941-CGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA-CGAGAGAGAGAGAGAGAGAGAGAGAGAGA

Variant names:

• chr11-128693941-CGAGAGAGAGA-C
• rs57930585
• ENST00000526269.2:n.112-560_112-551delTCTCTCTCTC

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+841_-82+850delGAGAGAGAGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 174,890 control chromosomes in the GnomAD database, including 210 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.076 (205 hom., cov: 0)
  • Exomes 𝑓: 0.069 (5 hom.)
• Consequence: FLI1 NM_001440369.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 11-128693941-CGAGAGAGAGA-C is Benign according to our data. Variant chr11-128693941-CGAGAGAGAGA-C is described in ClinVar as Benign. ClinVar VariationId is 1276147.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 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+841_-82+850delGAGAGAGAGA		intron	N/A	NP_001427298.1
	FLI1	NM_001440370.1		c.-82+8612_-82+8621delGAGAGAGAGA		intron	N/A	NP_001427299.1
	FLI1	NM_001440371.1		c.-82+1184_-82+1193delGAGAGAGAGA		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.112-560_112-551delTCTCTCTCTC		intron	N/A
	FLI1	ENST00000897157.1		c.-275_-266delGAGAGAGAGA		5_prime_UTR	Exon 1 of 10	ENSP00000567216.1
	FLI1	ENST00000897156.1		c.-275_-266delGAGAGAGAGA		5_prime_UTR	Exon 1 of 8	ENSP00000567215.1

Frequencies

GnomAD3 genomes AF: 0.0760 AC: 6289 AN: 82696 Hom.: 206 Cov.: 0

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0992

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.0286

Gnomad NFE AF: 0.0666

Gnomad OTH AF: 0.0630

GnomAD4 exome AF: 0.0693 AC: 6384 AN: 92170 Hom.: 5 AF XY: 0.0683 AC XY: 2988 AN XY: 43768

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

African (AFR) AF: 0.0861 AC: 333 AN: 3868

American (AMR) AF: 0.0839 AC: 226 AN: 2694

Ashkenazi Jewish (ASJ) AF: 0.0439 AC: 232 AN: 5282

East Asian (EAS) AF: 0.129 AC: 1462 AN: 11332

South Asian (SAS) AF: 0.0507 AC: 89 AN: 1756

European-Finnish (FIN) AF: 0.0996 AC: 197 AN: 1978

Middle Eastern (MID) AF: 0.0652 AC: 36 AN: 552

European-Non Finnish (NFE) AF: 0.0581 AC: 3339 AN: 57430

Other (OTH) AF: 0.0646 AC: 470 AN: 7278

⚠️ 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: 0.0760 AC: 6289 AN: 82720 Hom.: 205 Cov.: 0 AF XY: 0.0795 AC XY: 3032 AN XY: 38128

African (AFR) AF: 0.0779 AC: 1434 AN: 18408

American (AMR) AF: 0.0917 AC: 717 AN: 7818

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 115 AN: 2476

East Asian (EAS) AF: 0.125 AC: 337 AN: 2700

South Asian (SAS) AF: 0.0980 AC: 207 AN: 2112

European-Finnish (FIN) AF: 0.120 AC: 380 AN: 3176

Middle Eastern (MID) AF: 0.0299 AC: 4 AN: 134

European-Non Finnish (NFE) AF: 0.0666 AC: 2943 AN: 44162

Other (OTH) AF: 0.0640 AC: 75 AN: 1172

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		2.9
Mutation Taster		=296/4	polymorphism (auto)

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;