rs682695

Positions:

• chr11-128812565-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLI1	NM_002017.5	c.*1577C>A		3_prime_UTR_variant	9/9	ENST00000527786.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLI1	ENST00000527786.7	c.*1577C>A		3_prime_UTR_variant	9/9	1	NM_002017.5	P1
FLI1	ENST00000281428.12	c.*1577C>A		3_prime_UTR_variant	10/10	1
FLI1	ENST00000344954.10	c.*1577C>A		3_prime_UTR_variant	7/7	2
FLI1	ENST00000534087.3	c.*1577C>A		3_prime_UTR_variant	10/10	2

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

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.337

Gnomad4 SAS exome AF: 0.217

Gnomad4 FIN exome AF: 0.205

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.261

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

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.252

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs682695; hg19: chr11-128682460;