Variant 12-88079272-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.5227-43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 1,500,250 control chromosomes in the GnomAD database, including 618,300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 50393 hom., cov: 31)

Exomes 𝑓: 0.91 ( 567907 hom. )

Consequence

CEP290
NM_025114.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.34

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:

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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=-0.91).

BP6

Variant 12-88079272-C-T is Benign according to our data. Variant chr12-88079272-C-T is described in ClinVar as [Benign]. Clinvar id is 126261.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 linkuse as main transcript	c.5227-43G>A		intron_variant		ENST00000552810.6	NP_079390.3
LOC124902977	XR_007063393.1 linkuse as main transcript	n.887-3041C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP290	ENST00000552810.6 linkuse as main transcript	c.5227-43G>A		intron_variant		1	NM_025114.4	ENSP00000448012	P4

Frequencies

GnomAD3 genomes

AF:

0.781

AC:

118679

AN:

151890

Hom.:

50392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.410

Gnomad AMI

AF:

0.922

Gnomad AMR

AF:

0.866

Gnomad ASJ

AF:

0.895

Gnomad EAS

AF:

0.965

Gnomad SAS

AF:

0.897

Gnomad FIN

AF:

0.962

Gnomad MID

AF:

0.921

Gnomad NFE

AF:

0.928

Gnomad OTH

AF:

0.820

GnomAD3 exomes

AF:

0.896

AC:

157713

AN:

175992

Hom.:

72170

AF XY:

0.902

AC XY:

87411

AN XY:

96894

show subpopulations

Gnomad AFR exome

AF:

0.389

Gnomad AMR exome

AF:

0.923

Gnomad ASJ exome

AF:

0.905

Gnomad EAS exome

AF:

0.974

Gnomad SAS exome

AF:

0.888

Gnomad FIN exome

AF:

0.962

Gnomad NFE exome

AF:

0.928

Gnomad OTH exome

AF:

0.897

GnomAD4 exome

AF:

0.914

AC:

1232581

AN:

1348242

Hom.:

567907

Cov.:

AF XY:

0.914

AC XY:

613175

AN XY:

670568

show subpopulations

Gnomad4 AFR exome

AF:

0.395

Gnomad4 AMR exome

AF:

0.917

Gnomad4 ASJ exome

AF:

0.904

Gnomad4 EAS exome

AF:

0.952

Gnomad4 SAS exome

AF:

0.893

Gnomad4 FIN exome

AF:

0.961

Gnomad4 NFE exome

AF:

0.927

Gnomad4 OTH exome

AF:

0.890

GnomAD4 genome

AF:

0.781

AC:

118694

AN:

152008

Hom.:

50393

Cov.:

AF XY:

0.787

AC XY:

58484

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:

0.897

Gnomad4 FIN

AF:

0.962

Gnomad4 NFE

AF:

0.928

Gnomad4 OTH

AF:

0.822

Alfa

AF:

0.858

Hom.:

10701

Bravo

AF:

0.759

Asia WGS

AF:

0.882

AC:

3052

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.0020

DANN

Benign

0.58

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