11-128708262-T-C

Variant names:

• chr11-128708262-T-C
• rs619521
• NM_002017.5:c.18+13986T>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+13986T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,998 control chromosomes in the GnomAD database, including 13,290 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 0.42 (13290 hom., cov: 32)
• Consequence: FLI1 NM_002017.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLI1	NM_002017.5	c.18+13986T>C		intron_variant	Intron 1 of 8	ENST00000527786.7	NP_002008.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLI1	ENST00000527786.7	c.18+13986T>C		intron_variant	Intron 1 of 8	1	NM_002017.5	ENSP00000433488.2

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63155 AN: 151880 Hom.: 13282 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.416 AC: 63201 AN: 151998 Hom.: 13290 Cov.: 32 AF XY: 0.418 AC XY: 31056 AN XY: 74308

African (AFR) AF: 0.392 AC: 16245 AN: 41446

American (AMR) AF: 0.465 AC: 7102 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1365 AN: 3470

East Asian (EAS) AF: 0.256 AC: 1323 AN: 5172

South Asian (SAS) AF: 0.418 AC: 2015 AN: 4818

European-Finnish (FIN) AF: 0.449 AC: 4740 AN: 10566

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28956 AN: 67930

Other (OTH) AF: 0.411 AC: 869 AN: 2112

Alfa AF: 0.418 Hom.: 36115

Bravo AF: 0.412

Asia WGS AF: 0.353 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.50
PhyloP100		-0.20
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: rs619521; hg19: chr11-128578157;