rs496844

Variant names:

• chr11-128780134-C-G
• rs496844
• NM_002017.5:c.590-1824C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-128780134-C-G
• chr11-128780134-C-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.590-1824C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,074 control chromosomes in the GnomAD database, including 13,605 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 0.41 (13605 hom., cov: 33)
• Consequence: FLI1 NM_002017.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.5 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.590-1824C>G		intron	N/A	NP_002008.2
	FLI1	NM_001167681.3		c.491-1824C>G		intron	N/A	NP_001161153.1
	FLI1	NM_001440369.1		c.491-1824C>G		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.590-1824C>G		intron	N/A	ENSP00000433488.2
	FLI1	ENST00000429175.7	TSL:1	n.*512-1824C>G		intron	N/A	ENSP00000399985.3
	FLI1	ENST00000897157.1		c.590-1824C>G		intron	N/A	ENSP00000567216.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61623 AN: 151956 Hom.: 13591 Cov.: 33

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.405 AC: 61665 AN: 152074 Hom.: 13605 Cov.: 33 AF XY: 0.403 AC XY: 29975 AN XY: 74336

African (AFR) AF: 0.241 AC: 9984 AN: 41464

American (AMR) AF: 0.509 AC: 7789 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1885 AN: 3470

East Asian (EAS) AF: 0.315 AC: 1629 AN: 5170

South Asian (SAS) AF: 0.369 AC: 1776 AN: 4816

European-Finnish (FIN) AF: 0.384 AC: 4052 AN: 10562

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32887 AN: 67990

Other (OTH) AF: 0.485 AC: 1022 AN: 2108

Alfa AF: 0.425 Hom.: 1815

Bravo AF: 0.408

Asia WGS AF: 0.345 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.9
DANN	Benign	0.71
PhyloP100		0.12
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: rs496844; hg19: chr11-128650029;