Variant chr12-88083972-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_025114.4(CEP290):c.4705-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000843 in 1,437,000 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 1 hom. )

Consequence

CEP290
NM_025114.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.592

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 12-88083972-G-A is Benign according to our data. Variant chr12-88083972-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP290	NM_025114.4 linkuse as main transcript	c.4705-18C>T		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.4705-18C>T		intron_variant		1	NM_025114.4	ENSP00000448012.1		O15078

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000868

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000482

AC:

AN:

172066

Hom.:

AF XY:

0.000494

AC XY:

AN XY:

91110

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000210

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000763

Gnomad SAS exome

AF:

0.0000937

Gnomad FIN exome

AF:

0.0000562

Gnomad NFE exome

AF:

0.000990

Gnomad OTH exome

AF:

0.000649

GnomAD4 exome

AF:

0.000882

AC:

1133

AN:

1284794

Hom.:

Cov.:

AF XY:

0.000885

AC XY:

568

AN XY:

642004

show subpopulations

Gnomad4 AFR exome

AF:

0.000101

Gnomad4 AMR exome

AF:

0.000170

Gnomad4 ASJ exome

AF:

0.0000408

Gnomad4 EAS exome

AF:

0.0000266

Gnomad4 SAS exome

AF:

0.0000527

Gnomad4 FIN exome

AF:

0.0000795

Gnomad4 NFE exome

AF:

0.00111

Gnomad4 OTH exome

AF:

0.000609

GnomAD4 genome

AF:

0.000519

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000868

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000769

Hom.:

Bravo

AF:

0.000434

Asia WGS

AF:

0.00202

AC:

AN:

3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis;C0687120:Nephronophthisis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Senior-Loken syndrome 6;C1857780:Joubert syndrome 5;C1857821:Leber congenital amaurosis 10;C1970161:Meckel syndrome, type 4;C2673874:Bardet-Biedl syndrome 14

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.2

DANN

Benign

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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