Genetic Variant SENCR:n.112-491_112-490insC (chr11-128693881-T-TG) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001440369.1(FLI1):c.-82+746dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

FLI1
NM_001440369.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0940

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), ClinGen, Ambry Genetics

FLI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000109 (13/119752) while in subpopulation AMR AF = 0.000509 (6/11794). AF 95% confidence interval is 0.000221. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001440369.1. 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+746dupG	intron	N/A	NP_001427298.1
FLI1	NM_001440370.1	c.-82+8517dupG	intron	N/A	NP_001427299.1
FLI1	NM_001440371.1	c.-82+1089dupG	intron	N/A	NP_001427300.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SENCR	ENST00000526269.2	TSL:1	n.112-491_112-490insC	intron	N/A
FLI1	ENST00000696982.1		c.39+7180_39+7181insG	intron	N/A	ENSP00000513017.1	A0A8V8TM04
FLI1	ENST00000527767.7	TSL:4	c.-82+738_-82+739insG	intron	N/A	ENSP00000476428.1	V9GY62

Frequencies

GnomAD3 genomes

AF:

0.000109

AC:

AN:

119752

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000970

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000509

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:

0.0000692

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000228

AC:

AN:

92254

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

43772

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

4110

American (AMR)

AF:

0.00

AC:

AN:

2734

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5434

East Asian (EAS)

AF:

0.000274

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:

0.000298

AC:

AN:

57054

Other (OTH)

AF:

0.000136

AC:

AN:

7352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

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

AF:

0.000109

AC:

AN:

119752

Hom.:

Cov.:

AF XY:

0.0000705

AC XY:

AN XY:

56740

show subpopulations

African (AFR)

AF:

0.0000970

AC:

AN:

30932

American (AMR)

AF:

0.000509

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:

0.0000692

AC:

AN:

57790

Other (OTH)

AF:

0.00

AC:

AN:

1642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.094

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over