chr11-128693941-CGA-C

Variant names:

• chr11-128693941-CGA-C
• rs57930585
• ENST00000526269.2:n.112-552_112-551delTC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001440369.1(FLI1):​c.-82+849_-82+850delGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0695 in 171,746 control chromosomes in the GnomAD database, including 202 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.072 (200 hom., cov: 0)
  • Exomes 𝑓: 0.067 (2 hom.)
• Consequence: FLI1 NM_001440369.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.709
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0789 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+849_-82+850delGA		intron	N/A	NP_001427298.1
	FLI1	NM_001440370.1		c.-82+8620_-82+8621delGA		intron	N/A	NP_001427299.1
	FLI1	NM_001440371.1		c.-82+1192_-82+1193delGA		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.112-552_112-551delTC		intron	N/A
	FLI1	ENST00000897157.1		c.-267_-266delGA		5_prime_UTR	Exon 1 of 10	ENSP00000567216.1
	FLI1	ENST00000897156.1		c.-267_-266delGA		5_prime_UTR	Exon 1 of 8	ENSP00000567215.1

Frequencies

GnomAD3 genomes AF: 0.0725 AC: 5967 AN: 82360 Hom.: 199 Cov.: 0

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.0694

Gnomad AMR AF: 0.0600

Gnomad ASJ AF: 0.0792

Gnomad EAS AF: 0.0821

Gnomad SAS AF: 0.0542

Gnomad FIN AF: 0.0463

Gnomad MID AF: 0.0896

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.0893

GnomAD4 exome AF: 0.0668 AC: 5968 AN: 89364 Hom.: 2 AF XY: 0.0651 AC XY: 2767 AN XY: 42482

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

African (AFR) AF: 0.0743 AC: 277 AN: 3728

American (AMR) AF: 0.0627 AC: 167 AN: 2664

Ashkenazi Jewish (ASJ) AF: 0.0812 AC: 407 AN: 5012

East Asian (EAS) AF: 0.0672 AC: 745 AN: 11094

South Asian (SAS) AF: 0.0270 AC: 47 AN: 1742

European-Finnish (FIN) AF: 0.0213 AC: 42 AN: 1974

Middle Eastern (MID) AF: 0.0562 AC: 31 AN: 552

European-Non Finnish (NFE) AF: 0.0669 AC: 3715 AN: 55570

Other (OTH) AF: 0.0764 AC: 537 AN: 7028

⚠️ 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: 0.0724 AC: 5963 AN: 82382 Hom.: 200 Cov.: 0 AF XY: 0.0713 AC XY: 2707 AN XY: 37982

African (AFR) AF: 0.0601 AC: 1102 AN: 18344

American (AMR) AF: 0.0598 AC: 466 AN: 7788

Ashkenazi Jewish (ASJ) AF: 0.0792 AC: 196 AN: 2474

East Asian (EAS) AF: 0.0825 AC: 221 AN: 2678

South Asian (SAS) AF: 0.0542 AC: 114 AN: 2104

European-Finnish (FIN) AF: 0.0463 AC: 147 AN: 3174

Middle Eastern (MID) AF: 0.0923 AC: 12 AN: 130

European-Non Finnish (NFE) AF: 0.0811 AC: 3564 AN: 43960

Other (OTH) AF: 0.0873 AC: 102 AN: 1168

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.71
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs57930585; hg19: chr11-128563836;