11-128712662-T-C

Variant names:

• chr11-128712662-T-C
• rs665440
• NM_002017.5:c.18+18386T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002017.5(FLI1):​c.18+18386T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 152,146 control chromosomes in the GnomAD database, including 343 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.063 (343 hom., cov: 32)
• Consequence: FLI1 NM_002017.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• Publications: 6 publications found

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]

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0764 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002017.5. 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_002017.5	MANE Select	c.18+18386T>C		intron	N/A	NP_002008.2
	FLI1	NM_001167681.3		c.-136+18386T>C		intron	N/A	NP_001161153.1	Q01543-3
	FLI1	NM_001440369.1		c.-82+19519T>C		intron	N/A	NP_001427298.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLI1	ENST00000527786.7	TSL:1 MANE Select	c.18+18386T>C		intron	N/A	ENSP00000433488.2	Q01543-1
	FLI1	ENST00000429175.7	TSL:1	n.18+18386T>C		intron	N/A	ENSP00000399985.3	A0A0A0MSR4
	FLI1	ENST00000897157.1		c.18+18386T>C		intron	N/A	ENSP00000567216.1

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9593 AN: 152028 Hom.: 342 Cov.: 32

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0671

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.0411

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0620

Gnomad OTH AF: 0.0805

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0631 AC: 9601 AN: 152146 Hom.: 343 Cov.: 32 AF XY: 0.0600 AC XY: 4463 AN XY: 74396

African (AFR) AF: 0.0786 AC: 3263 AN: 41492

American (AMR) AF: 0.0670 AC: 1025 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00622 AC: 30 AN: 4820

European-Finnish (FIN) AF: 0.0411 AC: 435 AN: 10588

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0620 AC: 4212 AN: 67986

Other (OTH) AF: 0.0801 AC: 169 AN: 2110

Alfa AF: 0.0618 Hom.: 580

Bravo AF: 0.0657

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.58
PhyloP100		0.30
Mutation Taster		=100/0	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: rs665440; hg19: chr11-128582557;