NM_002017.5:c.19-7878C>T

Variant names:

• chr11-128750237-C-T
• rs590520
• NM_002017.5:c.19-7878C>T

Variant summary

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

The NM_002017.5(FLI1):​c.19-7878C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,066 control chromosomes in the GnomAD database, including 7,905 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 0.32 (7905 hom., cov: 32)
• Consequence: FLI1 NM_002017.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248
• Publications: 3 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=-0.5).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.414 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.19-7878C>T		intron	N/A	NP_002008.2
	FLI1	NM_001167681.3		c.-82+1947C>T		intron	N/A	NP_001161153.1
	FLI1	NM_001440369.1		c.-81-7878C>T		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.19-7878C>T		intron	N/A	ENSP00000433488.2
	FLI1	ENST00000281428.12	TSL:1	c.-351-7878C>T		intron	N/A	ENSP00000281428.8
	FLI1	ENST00000429175.7	TSL:1	n.19-7878C>T		intron	N/A	ENSP00000399985.3

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47868 AN: 151946 Hom.: 7889 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.315 AC: 47932 AN: 152066 Hom.: 7905 Cov.: 32 AF XY: 0.315 AC XY: 23426 AN XY: 74358

African (AFR) AF: 0.361 AC: 14950 AN: 41458

American (AMR) AF: 0.423 AC: 6468 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 998 AN: 3470

East Asian (EAS) AF: 0.305 AC: 1575 AN: 5170

South Asian (SAS) AF: 0.239 AC: 1149 AN: 4816

European-Finnish (FIN) AF: 0.248 AC: 2619 AN: 10572

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.282 AC: 19164 AN: 67976

Other (OTH) AF: 0.316 AC: 667 AN: 2112

Alfa AF: 0.298 Hom.: 18523

Bravo AF: 0.333

Asia WGS AF: 0.281 AC: 978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		0.25
Mutation Taster		=99/1	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: rs590520; hg19: chr11-128620132;