Genetic Variant ENST00000526269.2:n.112-492_112-491delCC (chr11-128693881-TGG-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000526269.2(SENCR):n.112-492_112-491delCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 92,250 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SENCR
ENST00000526269.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.95

Publications

1 publications found

Variant links:

Genes affected

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

SENCR links:

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]

FLI1 Gene-Disease associations (from GenCC):

bleeding disorder, platelet-type, 21
Inheritance: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

FLI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000526269.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
FLI1	NM_001440369.1	c.-82+745_-82+746delGG	intron	N/A	NP_001427298.1
FLI1	NM_001440370.1	c.-82+8516_-82+8517delGG	intron	N/A	NP_001427299.1
FLI1	NM_001440371.1	c.-82+1088_-82+1089delGG	intron	N/A	NP_001427300.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SENCR	ENST00000526269.2	TSL:1	n.112-492_112-491delCC	intron	N/A
FLI1	ENST00000696982.1		c.39+7181_39+7182delGG	intron	N/A	ENSP00000513017.1	A0A8V8TM04
FLI1	ENST00000527767.7	TSL:4	c.-82+739_-82+740delGG	intron	N/A	ENSP00000476428.1	V9GY62

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

119750

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000217

AC:

AN:

92250

Hom.:

AF XY:

0.00

AC XY:

AN XY:

43770

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000487

AC:

AN:

4110

American (AMR)

AF:

0.00

AC:

AN:

2734

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5434

East Asian (EAS)

AF:

0.00

AC:

AN:

10956

South Asian (SAS)

AF:

0.00

AC:

AN:

1894

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

576

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

57050

Other (OTH)

AF:

0.00

AC:

AN:

7352

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

119750

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

56740

African (AFR)

AF:

0.00

AC:

AN:

30932

American (AMR)

AF:

0.00

AC:

AN:

11794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3190

East Asian (EAS)

AF:

0.00

AC:

AN:

3998

South Asian (SAS)

AF:

0.00

AC:

AN:

3574

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5762

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

57788

Other (OTH)

AF:

0.00

AC:

AN:

1642

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.9

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over