11-128693881-TGGG-TGG

Variant names:

• chr11-128693881-TG-T
• rs55635129
• ENST00000526269.2:n.112-491delC

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+746delG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (33169 hom., cov: 0)
  • Exomes 𝑓: 0.74 (24563 hom.)
• Consequence: FLI1 NM_001440369.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0940
• Publications: 1 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 11-128693881-TG-T is Benign according to our data. Variant chr11-128693881-TG-T is described in ClinVar as Benign. ClinVar VariationId is 1241437.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 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+746delG		intron	N/A	NP_001427298.1
	FLI1	NM_001440370.1		c.-82+8517delG		intron	N/A	NP_001427299.1
	FLI1	NM_001440371.1		c.-82+1089delG		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.112-491delC		intron	N/A
	FLI1	ENST00000696982.1		c.39+7181delG		intron	N/A	ENSP00000513017.1	A0A8V8TM04
	FLI1	ENST00000527767.7	TSL:4	c.-82+739delG		intron	N/A	ENSP00000476428.1	V9GY62

Frequencies

GnomAD3 genomes AF: 0.774 AC: 92642 AN: 119640 Hom.: 33137 Cov.: 0

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.783

GnomAD4 exome AF: 0.743 AC: 68504 AN: 92218 Hom.: 24563 Cov.: 0 AF XY: 0.740 AC XY: 32379 AN XY: 43754

African (AFR) AF: 0.766 AC: 3147 AN: 4110

American (AMR) AF: 0.720 AC: 1968 AN: 2734

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 4478 AN: 5432

East Asian (EAS) AF: 0.718 AC: 7862 AN: 10946

South Asian (SAS) AF: 0.710 AC: 1344 AN: 1892

European-Finnish (FIN) AF: 0.591 AC: 1264 AN: 2138

Middle Eastern (MID) AF: 0.806 AC: 464 AN: 576

European-Non Finnish (NFE) AF: 0.742 AC: 42335 AN: 57040

Other (OTH) AF: 0.768 AC: 5642 AN: 7350

GnomAD4 genome AF: 0.774 AC: 92719 AN: 119732 Hom.: 33169 Cov.: 0 AF XY: 0.775 AC XY: 44005 AN XY: 56794

African (AFR) AF: 0.794 AC: 24616 AN: 30994

American (AMR) AF: 0.764 AC: 9016 AN: 11794

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2613 AN: 3190

East Asian (EAS) AF: 0.767 AC: 3053 AN: 3982

South Asian (SAS) AF: 0.783 AC: 2799 AN: 3576

European-Finnish (FIN) AF: 0.743 AC: 4276 AN: 5754

Middle Eastern (MID) AF: 0.851 AC: 223 AN: 262

European-Non Finnish (NFE) AF: 0.766 AC: 44206 AN: 57740

Other (OTH) AF: 0.781 AC: 1290 AN: 1652

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.660 AC: 2085 AN: 3160

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		-0.094
Mutation Taster		=300/0	polymorphism (auto)

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: rs55635129; hg19: chr11-128563776;