NM_002017.5:c.18+316A>C

Variant names:

• chr11-128694592-A-C
• rs11221436
• NM_002017.5:c.18+316A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002017.5(FLI1):​c.18+316A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 152,128 control chromosomes in the GnomAD database, including 76,048 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 1.0 (76048 hom., cov: 33)
• Consequence: FLI1 NM_002017.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.42
• Publications: 0 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]

SENCR (HGNC:44177): (smooth muscle and endothelial cell enriched migration/differentiation-associated lncRNA)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-128694592-A-C is Benign according to our data. Variant chr11-128694592-A-C is described in ClinVar as [Benign]. Clinvar id is 1227564.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLI1	NM_002017.5	c.18+316A>C		intron_variant	Intron 1 of 8	ENST00000527786.7	NP_002008.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLI1	ENST00000527786.7	c.18+316A>C		intron_variant	Intron 1 of 8	1	NM_002017.5	ENSP00000433488.2

Frequencies

GnomAD3 genomes AF: 1.00 AC: 151994 AN: 152010 Hom.: 75989 Cov.: 33

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

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

GnomAD4 genome AF: 1.00 AC: 152112 AN: 152128 Hom.: 76048 Cov.: 33 AF XY: 1.00 AC XY: 74376 AN XY: 74380

African (AFR) AF: 1.00 AC: 41546 AN: 41548

American (AMR) AF: 1.00 AC: 15306 AN: 15308

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3470 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5089 AN: 5090

South Asian (SAS) AF: 1.00 AC: 4829 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10608 AN: 10608

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 67946 AN: 67956

Other (OTH) AF: 1.00 AC: 2112 AN: 2112

Alfa AF: 1.00 Hom.: 2811

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.65
DANN	Benign	0.25
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11221436; hg19: chr11-128564487;