11-128757831-T-A

Position:

• chr11-128757831-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002017.5(FLI1):​c.19-284T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0516 in 152,164 control chromosomes in the GnomAD database, including 482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.052 (482 hom., cov: 31)
• Consequence: FLI1 NM_002017.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0250

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-128757831-T-A is Benign according to our data. Variant chr11-128757831-T-A is described in ClinVar as [Benign]. Clinvar id is 1246039.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLI1	NM_002017.5	c.19-284T>A		intron_variant		ENST00000527786.7	NP_002008.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLI1	ENST00000527786.7	c.19-284T>A		intron_variant		1	NM_002017.5	ENSP00000433488	P1

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7856 AN: 152046 Hom.: 481 Cov.: 31

Gnomad AFR AF: 0.0977

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0867

Gnomad ASJ AF: 0.00606

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.0672

Gnomad FIN AF: 0.0242

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00554

Gnomad OTH AF: 0.0398

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

GnomAD4 genome AF: 0.0516 AC: 7859 AN: 152164 Hom.: 482 Cov.: 31 AF XY: 0.0550 AC XY: 4090 AN XY: 74378

Gnomad4 AFR AF: 0.0976

Gnomad4 AMR AF: 0.0864

Gnomad4 ASJ AF: 0.00606

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.0667

Gnomad4 FIN AF: 0.0242

Gnomad4 NFE AF: 0.00554

Gnomad4 OTH AF: 0.0408

Alfa AF: 0.0296 Hom.: 19

Bravo AF: 0.0597

Asia WGS AF: 0.165 AC: 570 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.67

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: rs75901261; hg19: chr11-128627726;