11-128693941-CGAGAGA-C

Variant names:

• chr11-128693941-CGAGAGA-C
• rs57930585
• ENST00000526269.2:n.112-556_112-551delTCTCTC

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+845_-82+850delGAGAGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 172,806 control chromosomes in the GnomAD database, including 383 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (378 hom., cov: 0)
  • Exomes 𝑓: 0.11 (5 hom.)
• Consequence: FLI1 NM_001440369.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.49
• 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-CGAGAGA-C is Benign according to our data. Variant chr11-128693941-CGAGAGA-C is described in ClinVar as Benign. ClinVar VariationId is 1280517.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.112 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+845_-82+850delGAGAGA		intron	N/A	NP_001427298.1
	FLI1	NM_001440370.1		c.-82+8616_-82+8621delGAGAGA		intron	N/A	NP_001427299.1
	FLI1	NM_001440371.1		c.-82+1188_-82+1193delGAGAGA		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.112-556_112-551delTCTCTC		intron	N/A
	FLI1	ENST00000897157.1		c.-271_-266delGAGAGA		5_prime_UTR	Exon 1 of 10	ENSP00000567216.1
	FLI1	ENST00000897156.1		c.-271_-266delGAGAGA		5_prime_UTR	Exon 1 of 8	ENSP00000567215.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 9095 AN: 82508 Hom.: 377 Cov.: 0

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0883

Gnomad AMR AF: 0.0792

Gnomad ASJ AF: 0.0990

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0714

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.112 AC: 10141 AN: 90276 Hom.: 5 AF XY: 0.110 AC XY: 4717 AN XY: 42812

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

African (AFR) AF: 0.118 AC: 449 AN: 3810

American (AMR) AF: 0.111 AC: 295 AN: 2656

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 543 AN: 5152

East Asian (EAS) AF: 0.122 AC: 1362 AN: 11154

South Asian (SAS) AF: 0.0608 AC: 105 AN: 1726

European-Finnish (FIN) AF: 0.0813 AC: 160 AN: 1968

Middle Eastern (MID) AF: 0.121 AC: 67 AN: 552

European-Non Finnish (NFE) AF: 0.113 AC: 6331 AN: 56112

Other (OTH) AF: 0.116 AC: 829 AN: 7146

⚠️ 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: 0.110 AC: 9096 AN: 82530 Hom.: 378 Cov.: 0 AF XY: 0.109 AC XY: 4143 AN XY: 38054

African (AFR) AF: 0.109 AC: 2001 AN: 18398

American (AMR) AF: 0.0790 AC: 617 AN: 7806

Ashkenazi Jewish (ASJ) AF: 0.0990 AC: 245 AN: 2474

East Asian (EAS) AF: 0.117 AC: 316 AN: 2698

South Asian (SAS) AF: 0.118 AC: 249 AN: 2108

European-Finnish (FIN) AF: 0.142 AC: 450 AN: 3174

Middle Eastern (MID) AF: 0.0746 AC: 10 AN: 134

European-Non Finnish (NFE) AF: 0.115 AC: 5039 AN: 43998

Other (OTH) AF: 0.101 AC: 119 AN: 1174

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		=297/3	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;