11-128694899-A-C

Variant names:

• chr11-128694899-A-C
• rs7930515
• NM_002017.5:c.18+623A>C

Variant summary

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

The NM_002017.5(FLI1):​c.18+623A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 152,032 control chromosomes in the GnomAD database, including 38,492 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 0.71 (38492 hom., cov: 34)
• Consequence: FLI1 NM_002017.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.667
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLI1	NM_002017.5	c.18+623A>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+623A>C		intron_variant	Intron 1 of 8	1	NM_002017.5	ENSP00000433488.2

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107989 AN: 151922 Hom.: 38455 Cov.: 34

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.711 AC: 108080 AN: 152032 Hom.: 38492 Cov.: 34 AF XY: 0.709 AC XY: 52676 AN XY: 74324

African (AFR) AF: 0.751 AC: 31149 AN: 41494

American (AMR) AF: 0.697 AC: 10661 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2761 AN: 3470

East Asian (EAS) AF: 0.679 AC: 3480 AN: 5122

South Asian (SAS) AF: 0.682 AC: 3291 AN: 4828

European-Finnish (FIN) AF: 0.652 AC: 6919 AN: 10604

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47343 AN: 67896

Other (OTH) AF: 0.719 AC: 1521 AN: 2114

Alfa AF: 0.706 Hom.: 125420

Bravo AF: 0.716

Asia WGS AF: 0.677 AC: 2351 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.7
DANN	Benign	0.57
PhyloP100		-0.67
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: rs7930515; hg19: chr11-128564794;