NM_002017.5:c.230+1440C>A

Variant names:

• chr11-128759766-C-A
• rs670809
• NM_002017.5:c.230+1440C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002017.5(FLI1):​c.230+1440C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000512 in 152,228 control chromosomes in the GnomAD database, including 2 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 0.00051 (2 hom., cov: 32)
• Consequence: FLI1 NM_002017.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• 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: 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=-0.87).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000512 (78/152228) while in subpopulation SAS AF = 0.0149 (72/4826). AF 95% confidence interval is 0.0121. There are 2 homozygotes in GnomAd4. There are 60 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

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.230+1440C>A		intron	N/A	NP_002008.2
	FLI1	NM_001167681.3		c.131+1440C>A		intron	N/A	NP_001161153.1	Q01543-3
	FLI1	NM_001440369.1		c.131+1440C>A		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.230+1440C>A		intron	N/A	ENSP00000433488.2	Q01543-1
	FLI1	ENST00000429175.7	TSL:1	n.230+1440C>A		intron	N/A	ENSP00000399985.3	A0A0A0MSR4
	FLI1	ENST00000897157.1		c.230+1440C>A		intron	N/A	ENSP00000567216.1

Frequencies

GnomAD3 genomes AF: 0.000506 AC: 77 AN: 152110 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

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

GnomAD4 genome AF: 0.000512 AC: 78 AN: 152228 Hom.: 2 Cov.: 32 AF XY: 0.000806 AC XY: 60 AN XY: 74416

African (AFR) AF: 0.0000241 AC: 1 AN: 41538

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.0149 AC: 72 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68010

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00 Hom.: 13976

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.39
DANN	Benign	0.58
PhyloP100		-0.014

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: rs670809; hg19: chr11-128629661;