Variant 12-88103061-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025114.4(CEP290):c.2818-50G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 1,280,644 control chromosomes in the GnomAD database, including 526,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 50396 hom., cov: 31)

Exomes 𝑓: 0.92 ( 476443 hom. )

Consequence

CEP290
NM_025114.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.639

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 12-88103061-C-G is Benign according to our data. Variant chr12-88103061-C-G is described in ClinVar as [Benign]. Clinvar id is 126253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP290	NM_025114.4 link	c.2818-50G>C		intron_variant		ENST00000552810.6	NP_079390.3	O15078Q05BJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP290	ENST00000552810.6 link	c.2818-50G>C		intron_variant		1	NM_025114.4	ENSP00000448012.1		O15078

Frequencies

GnomAD3 genomes

AF:

0.781

AC:

118678

AN:

151884

Hom.:

50394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.410

Gnomad AMI

AF:

0.923

Gnomad AMR

AF:

0.866

Gnomad ASJ

AF:

0.895

Gnomad EAS

AF:

0.965

Gnomad SAS

AF:

0.898

Gnomad FIN

AF:

0.963

Gnomad MID

AF:

0.921

Gnomad NFE

AF:

0.928

Gnomad OTH

AF:

0.821

GnomAD3 exomes

AF:

0.904

AC:

68734

AN:

76008

Hom.:

31574

AF XY:

0.910

AC XY:

38022

AN XY:

41794

show subpopulations

Gnomad AFR exome

AF:

0.399

Gnomad AMR exome

AF:

0.904

Gnomad ASJ exome

AF:

0.908

Gnomad EAS exome

AF:

0.969

Gnomad SAS exome

AF:

0.887

Gnomad FIN exome

AF:

0.963

Gnomad NFE exome

AF:

0.927

Gnomad OTH exome

AF:

0.904

GnomAD4 exome

AF:

0.916

AC:

1033778

AN:

1128642

Hom.:

476443

Cov.:

AF XY:

0.916

AC XY:

509847

AN XY:

556586

show subpopulations

Gnomad4 AFR exome

AF:

0.410

Gnomad4 AMR exome

AF:

0.900

Gnomad4 ASJ exome

AF:

0.903

Gnomad4 EAS exome

AF:

0.948

Gnomad4 SAS exome

AF:

0.892

Gnomad4 FIN exome

AF:

0.961

Gnomad4 NFE exome

AF:

0.928

Gnomad4 OTH exome

AF:

0.891

GnomAD4 genome

AF:

0.781

AC:

118694

AN:

152002

Hom.:

50396

Cov.:

AF XY:

0.787

AC XY:

58488

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.410

Gnomad4 AMR

AF:

0.866

Gnomad4 ASJ

AF:

0.895

Gnomad4 EAS

AF:

0.965

Gnomad4 SAS

AF:

0.899

Gnomad4 FIN

AF:

0.963

Gnomad4 NFE

AF:

0.928

Gnomad4 OTH

AF:

0.822

Alfa

AF:

0.856

Hom.:

9636

Bravo

AF:

0.759

Asia WGS

AF:

0.880

AC:

3055

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Senior-Loken syndrome 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Bardet-Biedl syndrome 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Meckel syndrome, type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Joubert syndrome 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.2

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

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