Variant 12-88059831-C-T 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.6645+67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 1,324,504 control chromosomes in the GnomAD database, including 590,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 65636 hom., cov: 33)

Exomes 𝑓: 0.95 ( 525064 hom. )

Consequence

CEP290
NM_025114.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0210

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:

CEP290 (HGNC:):

CEP290 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 12-88059831-C-T is Benign according to our data. Variant chr12-88059831-C-T is described in ClinVar as [Benign]. Clinvar id is 1209819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP290	NM_025114.4 linkuse as main transcript	c.6645+67G>A		intron_variant		ENST00000552810.6	NP_079390.3	O15078Q05BJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP290	ENST00000552810.6 linkuse as main transcript	c.6645+67G>A		intron_variant		1	NM_025114.4	ENSP00000448012.1		O15078

Frequencies

GnomAD3 genomes

AF:

0.928

AC:

141164

AN:

152148

Hom.:

65602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.873

Gnomad AMI

AF:

0.953

Gnomad AMR

AF:

0.938

Gnomad ASJ

AF:

0.895

Gnomad EAS

AF:

0.987

Gnomad SAS

AF:

0.905

Gnomad FIN

AF:

0.988

Gnomad MID

AF:

0.949

Gnomad NFE

AF:

0.948

Gnomad OTH

AF:

0.932

GnomAD4 exome

AF:

0.946

AC:

1109143

AN:

1172238

Hom.:

525064

AF XY:

0.945

AC XY:

551611

AN XY:

583818

show subpopulations

Gnomad4 AFR exome

AF:

0.873

Gnomad4 AMR exome

AF:

0.954

Gnomad4 ASJ exome

AF:

0.907

Gnomad4 EAS exome

AF:

0.992

Gnomad4 SAS exome

AF:

0.904

Gnomad4 FIN exome

AF:

0.984

Gnomad4 NFE exome

AF:

0.949

Gnomad4 OTH exome

AF:

0.936

GnomAD4 genome

AF:

0.928

AC:

141252

AN:

152266

Hom.:

65636

Cov.:

AF XY:

0.930

AC XY:

69224

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.872

Gnomad4 AMR

AF:

0.938

Gnomad4 ASJ

AF:

0.895

Gnomad4 EAS

AF:

0.987

Gnomad4 SAS

AF:

0.906

Gnomad4 FIN

AF:

0.988

Gnomad4 NFE

AF:

0.948

Gnomad4 OTH

AF:

0.932

Alfa

AF:

0.939

Hom.:

67936

Bravo

AF:

0.923

Asia WGS

AF:

0.928

AC:

3228

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

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

-0.95

CADD

Benign

6.4

DANN

Benign

0.50

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.

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