NM_002017.5:c.*1577C>A

Variant names:

• chr11-128812565-C-A
• rs682695
• NM_002017.5:c.*1577C>A

Variant summary

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

The NM_002017.5(FLI1):​c.*1577C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 223,138 control chromosomes in the GnomAD database, including 8,420 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 0.25 (5304 hom., cov: 33)
  • Exomes 𝑓: 0.29 (3116 hom.)
• Consequence: FLI1 NM_002017.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263
• 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 (NFE) allele frequency at 95% confidence interval = 0.32 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.*1577C>A		3_prime_UTR	Exon 9 of 9	NP_002008.2
	FLI1	NM_001167681.3		c.*1577C>A		3_prime_UTR	Exon 10 of 10	NP_001161153.1
	FLI1	NM_001440369.1		c.*1577C>A		3_prime_UTR	Exon 9 of 9	NP_001427298.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLI1	ENST00000527786.7	TSL:1 MANE Select	c.*1577C>A		3_prime_UTR	Exon 9 of 9	ENSP00000433488.2
	FLI1	ENST00000534087.3	TSL:2	c.*1577C>A		3_prime_UTR	Exon 10 of 10	ENSP00000432950.1
	FLI1	ENST00000429175.7	TSL:1	n.*2858C>A		downstream_gene	N/A	ENSP00000399985.3

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38245 AN: 151958 Hom.: 5300 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.291 AC: 20650 AN: 71062 Hom.: 3116 Cov.: 0 AF XY: 0.291 AC XY: 9537 AN XY: 32784

African (AFR) AF: 0.112 AC: 382 AN: 3426

American (AMR) AF: 0.211 AC: 448 AN: 2122

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 959 AN: 4502

East Asian (EAS) AF: 0.337 AC: 3439 AN: 10194

South Asian (SAS) AF: 0.217 AC: 139 AN: 640

European-Finnish (FIN) AF: 0.205 AC: 9 AN: 44

Middle Eastern (MID) AF: 0.260 AC: 116 AN: 446

European-Non Finnish (NFE) AF: 0.311 AC: 13609 AN: 43754

Other (OTH) AF: 0.261 AC: 1549 AN: 5934

GnomAD4 genome AF: 0.252 AC: 38262 AN: 152076 Hom.: 5304 Cov.: 33 AF XY: 0.251 AC XY: 18663 AN XY: 74318

African (AFR) AF: 0.126 AC: 5235 AN: 41498

American (AMR) AF: 0.220 AC: 3359 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 709 AN: 3464

East Asian (EAS) AF: 0.253 AC: 1305 AN: 5168

South Asian (SAS) AF: 0.233 AC: 1121 AN: 4812

European-Finnish (FIN) AF: 0.337 AC: 3555 AN: 10552

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.324 AC: 22030 AN: 67978

Other (OTH) AF: 0.252 AC: 533 AN: 2112

Alfa AF: 0.290 Hom.: 902

Bravo AF: 0.237

Asia WGS AF: 0.228 AC: 793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.68
PhyloP100		0.26
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: rs682695; hg19: chr11-128682460;