11-128693941-CGAGAGA-C

Variant names:

• chr11-128693941-CGAGAGA-C
• rs57930585
• ENST00000281428:c.-640_-635delGAGAGA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000281428(FLI1):​c.-640_-635delGAGAGA variant causes a 5 prime UTR 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 ENST00000281428 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.49

Genes affected

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]

SENCR (HGNC:44177): (smooth muscle and endothelial cell enriched migration/differentiation-associated lncRNA)

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLI1	NM_001271012.2	c.-203+7287_-203+7292delGAGAGA		intron_variant	Intron 1 of 6		NP_001257941.1
FLI1	XM_011542701.3	c.-82+845_-82+850delGAGAGA		intron_variant	Intron 1 of 8		XP_011541003.1
FLI1	XM_017017405.2	c.-82+8616_-82+8621delGAGAGA		intron_variant	Intron 1 of 8		XP_016872894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLI1	ENST00000281428	c.-640_-635delGAGAGA		5_prime_UTR_variant	Exon 1 of 10	1		ENSP00000281428.8
SENCR	ENST00000526269.2	n.112-556_112-551delTCTCTC		intron_variant	Intron 1 of 2	1
FLI1	ENST00000696982.1	c.39+7287_39+7292delGAGAGA		intron_variant	Intron 1 of 8			ENSP00000513017.1

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

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.0608

Gnomad4 FIN exome AF: 0.0813

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.110 AC: 9096 AN: 82530 Hom.: 378 Cov.: 0 AF XY: 0.109 AC XY: 4143 AN XY: 38054

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0790

Gnomad4 ASJ AF: 0.0990

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.101

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs57930585; hg19: chr11-128563836;