11-128694294-G-T

Variant names:

• chr11-128694294-G-T
• rs201691053
• NM_002017.5:c.18+18G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002017.5(FLI1):​c.18+18G>T variant causes a intron change. The variant allele was found at a frequency of 0.000336 in 1,357,174 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: FLI1 NM_002017.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.92
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 11-128694294-G-T is Benign according to our data. Variant chr11-128694294-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1971297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00159 (242/152318) while in subpopulation AFR AF = 0.00539 (224/41574). AF 95% confidence interval is 0.00481. There are 2 homozygotes in GnomAd4. There are 120 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00159 AC: 242 AN: 152202 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00540

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000440 AC: 43 AN: 97694 AF XY: 0.000358

Gnomad AFR exome AF: 0.00606

Gnomad AMR exome AF: 0.000120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000193

Gnomad OTH exome AF: 0.000589

GnomAD4 exome AF: 0.000178 AC: 214 AN: 1204856 Hom.: 0 Cov.: 31 AF XY: 0.000159 AC XY: 93 AN XY: 583290

African (AFR) AF: 0.00590 AC: 148 AN: 25104

American (AMR) AF: 0.000354 AC: 6 AN: 16950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16450

East Asian (EAS) AF: 0.00 AC: 0 AN: 30114

South Asian (SAS) AF: 0.00 AC: 0 AN: 44008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43336

Middle Eastern (MID) AF: 0.000648 AC: 3 AN: 4628

European-Non Finnish (NFE) AF: 0.0000451 AC: 44 AN: 976302

Other (OTH) AF: 0.000271 AC: 13 AN: 47964

GnomAD4 genome AF: 0.00159 AC: 242 AN: 152318 Hom.: 2 Cov.: 33 AF XY: 0.00161 AC XY: 120 AN XY: 74478

African (AFR) AF: 0.00539 AC: 224 AN: 41574

American (AMR) AF: 0.000784 AC: 12 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68016

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00202

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Nov 25, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Dec 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely 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	-0.50
CADD	Benign	15
DANN	Benign	0.84
PhyloP100		3.9
PromoterAI		-0.0048	Neutral
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs201691053; hg19: chr11-128564189;