chr11-128693941-CGAGAGAGAGAGAGAGA-C

Variant names:

• chr11-128693941-CGAGAGAGAGAGAGAGA-C
• rs57930585
• ENST00000281428:c.-650_-635delGAGAGAGAGAGAGAGA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000281428(FLI1):​c.-650_-635delGAGAGAGAGAGAGAGA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 176,460 control chromosomes in the GnomAD database, including 38 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.025 (36 hom., cov: 0)
  • Exomes 𝑓: 0.020 (2 hom.)
• Consequence: FLI1 ENST00000281428 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0252 (2089/82824) while in subpopulation AFR AF= 0.0484 (892/18420). AF 95% confidence interval is 0.0458. There are 36 homozygotes in gnomad4. There are 969 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 36 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLI1	NM_002017.5	c.-317_-302delGAGAGAGAGAGAGAGA		upstream_gene_variant		ENST00000527786.7	NP_002008.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLI1	ENST00000527786.7	c.-317_-302delGAGAGAGAGAGAGAGA		upstream_gene_variant		1	NM_002017.5	ENSP00000433488.2

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 2083 AN: 82800 Hom.: 36 Cov.: 0

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.00177

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.00845

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.0461

Gnomad MID AF: 0.00714

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.0285

GnomAD4 exome AF: 0.0203 AC: 1904 AN: 93636 Hom.: 2 AF XY: 0.0206 AC XY: 914 AN XY: 44440

Gnomad4 AFR exome AF: 0.0303

Gnomad4 AMR exome AF: 0.0219

Gnomad4 ASJ exome AF: 0.0138

Gnomad4 EAS exome AF: 0.0112

Gnomad4 SAS exome AF: 0.0164

Gnomad4 FIN exome AF: 0.0446

Gnomad4 NFE exome AF: 0.0215

Gnomad4 OTH exome AF: 0.0190

GnomAD4 genome AF: 0.0252 AC: 2089 AN: 82824 Hom.: 36 Cov.: 0 AF XY: 0.0254 AC XY: 969 AN XY: 38172

Gnomad4 AFR AF: 0.0484

Gnomad4 AMR AF: 0.0132

Gnomad4 ASJ AF: 0.00845

Gnomad4 EAS AF: 0.0156

Gnomad4 SAS AF: 0.0161

Gnomad4 FIN AF: 0.0461

Gnomad4 NFE AF: 0.0184

Gnomad4 OTH AF: 0.0282

ClinVar

Not reported in ClinVar

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;