Genetic Variant CEP290:c.6522+12dupT (chr12-88060817-T-TA) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_025114.4(CEP290):c.6522+12dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 1,417,558 control chromosomes in the GnomAD database, including 566,175 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 50000 hom., cov: 0)

Exomes 𝑓: 0.90 ( 516175 hom. )

Consequence

CEP290
NM_025114.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:16

Conservation

PhyloP100: -0.206

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 links:

LOC124902977 (HGNC:):

LOC124902977 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 12-88060817-T-TA is Benign according to our data. Variant chr12-88060817-T-TA is described in ClinVar as [Benign]. Clinvar id is 166828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP290	NM_025114.4 link	c.6522+12dupT		intron_variant	Intron 47 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.6522+12_6522+13insT		intron_variant	Intron 47 of 53	1	NM_025114.4	ENSP00000448012.1		O15078

Frequencies

GnomAD3 genomes

AF:

0.779

AC:

118028

AN:

151442

Hom.:

50000

Cov.:

show subpopulations

Gnomad AFR

AF:

0.409

Gnomad AMI

AF:

0.921

Gnomad AMR

AF:

0.865

Gnomad ASJ

AF:

0.894

Gnomad EAS

AF:

0.962

Gnomad SAS

AF:

0.896

Gnomad FIN

AF:

0.962

Gnomad MID

AF:

0.921

Gnomad NFE

AF:

0.925

Gnomad OTH

AF:

0.818

GnomAD3 exomes

AF:

0.882

AC:

98803

AN:

112070

Hom.:

44531

AF XY:

0.889

AC XY:

52830

AN XY:

59444

show subpopulations

Gnomad AFR exome

AF:

0.379

Gnomad AMR exome

AF:

0.885

Gnomad ASJ exome

AF:

0.897

Gnomad EAS exome

AF:

0.959

Gnomad SAS exome

AF:

0.877

Gnomad FIN exome

AF:

0.958

Gnomad NFE exome

AF:

0.917

Gnomad OTH exome

AF:

0.879

GnomAD4 exome

AF:

0.899

AC:

1138572

AN:

1266002

Hom.:

516175

Cov.:

AF XY:

0.900

AC XY:

563370

AN XY:

625892

show subpopulations

Gnomad4 AFR exome

AF:

0.379

Gnomad4 AMR exome

AF:

0.883

Gnomad4 ASJ exome

AF:

0.892

Gnomad4 EAS exome

AF:

0.941

Gnomad4 SAS exome

AF:

0.880

Gnomad4 FIN exome

AF:

0.955

Gnomad4 NFE exome

AF:

0.913

Gnomad4 OTH exome

AF:

0.876

GnomAD4 genome

AF:

0.779

AC:

118041

AN:

151556

Hom.:

50000

Cov.:

AF XY:

0.785

AC XY:

58136

AN XY:

74056

show subpopulations

Gnomad4 AFR

AF:

0.408

Gnomad4 AMR

AF:

0.865

Gnomad4 ASJ

AF:

0.894

Gnomad4 EAS

AF:

0.962

Gnomad4 SAS

AF:

0.897

Gnomad4 FIN

AF:

0.962

Gnomad4 NFE

AF:

0.925

Gnomad4 OTH

AF:

0.819

Asia WGS

AF:

0.880

AC:

3030

AN:

3446

ClinVar

Significance: Benign

Submissions summary: Benign:16

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 16, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

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

- -

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

Mar 03, 2015

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;C0431399:Familial aplasia of the vermis;C0687120:Nephronophthisis

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Meckel syndrome, type 4

Benign:1

Jul 22, 2021

Genome-Nilou Lab

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

- -

Familial aplasia of the vermis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

12-88060817-TAA-TAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over