chr12-88129046-A-AC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_025114.4(CEP290):c.853-12_853-11insG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59819 hom., cov: 0)

Exomes 𝑓: 0.94 ( 597901 hom. )

Consequence

CEP290
NM_025114.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 1.17

Publications

5 publications found

Variant links:

Genes affected

CEP290 (HGNC:29021): (centrosomal protein 290) This gene encodes a protein with 13 putative coiled-coil domains, a region with homology to SMC chromosome segregation ATPases, six KID motifs, three tropomyosin homology domains and an ATP/GTP binding site motif A. The protein is localized to the centrosome and cilia and has sites for N-glycosylation, tyrosine sulfation, phosphorylation, N-myristoylation, and amidation. Mutations in this gene have been associated with Joubert syndrome and nephronophthisis and the presence of antibodies against this protein is associated with several forms of cancer. [provided by RefSeq, Jul 2008]

CEP290 Gene-Disease associations (from GenCC):

CEP290-related ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Joubert syndrome 5
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Bardet-Biedl syndrome 14
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
Leber congenital amaurosis 10
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Leber congenital amaurosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Joubert syndrome with oculorenal defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Meckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Senior-Loken syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CEP290 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 12-88129046-A-AC is Benign according to our data. Variant chr12-88129046-A-AC is described in ClinVar as [Benign]. Clinvar id is 166839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP290	NM_025114.4 link	c.853-12_853-11insG		intron_variant	Intron 10 of 53	ENST00000552810.6	NP_079390.3	O15078Q05BJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP290	ENST00000552810.6 link	c.853-12_853-11insG		intron_variant	Intron 10 of 53	1	NM_025114.4	ENSP00000448012.1		O15078

Frequencies

GnomAD3 genomes

AF:

0.881

AC:

133721

AN:

151716

Hom.:

59805

Cov.:

show subpopulations

Gnomad AFR

AF:

0.712

Gnomad AMI

AF:

0.953

Gnomad AMR

AF:

0.919

Gnomad ASJ

AF:

0.896

Gnomad EAS

AF:

0.988

Gnomad SAS

AF:

0.901

Gnomad FIN

AF:

0.988

Gnomad MID

AF:

0.937

Gnomad NFE

AF:

0.947

Gnomad OTH

AF:

0.893

GnomAD2 exomes

AF:

0.930

AC:

147491

AN:

158650

AF XY:

0.931

show subpopulations

Gnomad AFR exome

AF:

0.688

Gnomad AMR exome

AF:

0.945

Gnomad ASJ exome

AF:

0.904

Gnomad EAS exome

AF:

0.990

Gnomad FIN exome

AF:

0.986

Gnomad NFE exome

AF:

0.949

Gnomad OTH exome

AF:

0.923

GnomAD4 exome

AF:

0.942

AC:

1267255

AN:

1345980

Hom.:

597901

Cov.:

AF XY:

0.941

AC XY:

626919

AN XY:

666494

show subpopulations

African (AFR)

AF:

0.706

AC:

19607

AN:

27782

American (AMR)

AF:

0.943

AC:

23062

AN:

24450

Ashkenazi Jewish (ASJ)

AF:

0.904

AC:

20850

AN:

23064

East Asian (EAS)

AF:

0.993

AC:

34239

AN:

34492

South Asian (SAS)

AF:

0.895

AC:

58630

AN:

65524

European-Finnish (FIN)

AF:

0.984

AC:

47670

AN:

48434

Middle Eastern (MID)

AF:

0.914

AC:

4944

AN:

5410

European-Non Finnish (NFE)

AF:

0.949

AC:

1006843

AN:

1061296

Other (OTH)

AF:

0.926

AC:

51410

AN:

55528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3270

6541

9811

13082

16352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.881

AC:

133775

AN:

151830

Hom.:

59819

Cov.:

AF XY:

0.885

AC XY:

65672

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.712

AC:

29479

AN:

41432

American (AMR)

AF:

0.919

AC:

14013

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.896

AC:

3107

AN:

3468

East Asian (EAS)

AF:

0.988

AC:

5125

AN:

5186

South Asian (SAS)

AF:

0.902

AC:

4351

AN:

4824

European-Finnish (FIN)

AF:

0.988

AC:

10430

AN:

10556

Middle Eastern (MID)

AF:

0.932

AC:

272

AN:

292

European-Non Finnish (NFE)

AF:

0.947

AC:

64245

AN:

67812

Other (OTH)

AF:

0.894

AC:

1884

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

733

1466

2198

2931

3664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.910

Hom.:

7182

Bravo

AF:

0.869

Asia WGS

AF:

0.915

AC:

3153

AN:

3448

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jan 27, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Senior-Loken syndrome 6

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joubert syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Meckel-Gruber syndrome;C0431399:Joubert syndrome;C0687120:Nephronophthisis

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Leber congenital amaurosis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jun 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bardet-Biedl syndrome 14

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Meckel-Gruber syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Renal dysplasia and retinal aplasia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Meckel syndrome, type 4

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bardet-Biedl syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joubert syndrome 5

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=26/74

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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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chr12-88129046-A-AC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over