11-128758861-T-C

Variant names:

• chr11-128758861-T-C
• rs531894
• NM_002017.5:c.230+535T>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.230+535T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,984 control chromosomes in the GnomAD database, including 14,525 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 0.43 (14525 hom., cov: 31)
• Consequence: FLI1 NM_002017.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.922
• Publications: 2 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: AD, AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLI1	NM_002017.5	MANE Select	c.230+535T>C		intron	N/A	NP_002008.2
	FLI1	NM_001167681.3		c.131+535T>C		intron	N/A	NP_001161153.1
	FLI1	NM_001440369.1		c.131+535T>C		intron	N/A	NP_001427298.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLI1	ENST00000527786.7	TSL:1 MANE Select	c.230+535T>C		intron	N/A	ENSP00000433488.2
	FLI1	ENST00000429175.7	TSL:1	n.230+535T>C		intron	N/A	ENSP00000399985.3
	FLI1	ENST00000897157.1		c.230+535T>C		intron	N/A	ENSP00000567216.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65817 AN: 151866 Hom.: 14532 Cov.: 31

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.433 AC: 65838 AN: 151984 Hom.: 14525 Cov.: 31 AF XY: 0.438 AC XY: 32539 AN XY: 74246

African (AFR) AF: 0.437 AC: 18114 AN: 41458

American (AMR) AF: 0.389 AC: 5948 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1371 AN: 3466

East Asian (EAS) AF: 0.642 AC: 3296 AN: 5136

South Asian (SAS) AF: 0.506 AC: 2439 AN: 4816

European-Finnish (FIN) AF: 0.483 AC: 5095 AN: 10558

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28096 AN: 67956

Other (OTH) AF: 0.425 AC: 898 AN: 2112

Alfa AF: 0.437 Hom.: 2129

Bravo AF: 0.424

Asia WGS AF: 0.552 AC: 1920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.83
DANN	Benign	0.36
PhyloP100		-0.92
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: rs531894; hg19: chr11-128628756;