Variant 12-88111649-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_025114.4(CEP290):c.2217+45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00741 in 1,467,974 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 51 hom. )

Consequence

CEP290
NM_025114.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.964

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=-0.77).

BP6

Variant 12-88111649-A-G is Benign according to our data. Variant chr12-88111649-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 261834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-88111649-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00634 (965/152270) while in subpopulation NFE AF= 0.00875 (595/68002). AF 95% confidence interval is 0.00817. There are 6 homozygotes in gnomad4. There are 483 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP290	NM_025114.4 linkuse as main transcript	c.2217+45T>C		intron_variant		ENST00000552810.6	NP_079390.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP290	ENST00000552810.6 linkuse as main transcript	c.2217+45T>C		intron_variant		1	NM_025114.4	ENSP00000448012	P4

Frequencies

GnomAD3 genomes

AF:

0.00634

AC:

965

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00780

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00878

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00875

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00729

AC:

1209

AN:

165742

Hom.:

AF XY:

0.00780

AC XY:

728

AN XY:

93362

show subpopulations

Gnomad AFR exome

AF:

0.00119

Gnomad AMR exome

AF:

0.00555

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00390

Gnomad FIN exome

AF:

0.00874

Gnomad NFE exome

AF:

0.00925

Gnomad OTH exome

AF:

0.00872

GnomAD4 exome

AF:

0.00753

AC:

9908

AN:

1315704

Hom.:

Cov.:

AF XY:

0.00754

AC XY:

4934

AN XY:

654774

show subpopulations

Gnomad4 AFR exome

AF:

0.00115

Gnomad4 AMR exome

AF:

0.00625

Gnomad4 ASJ exome

AF:

0.0109

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00394

Gnomad4 FIN exome

AF:

0.00933

Gnomad4 NFE exome

AF:

0.00804

Gnomad4 OTH exome

AF:

0.00742

GnomAD4 genome

AF:

0.00634

AC:

965

AN:

152270

Hom.:

Cov.:

AF XY:

0.00649

AC XY:

483

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00779

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.00878

Gnomad4 NFE

AF:

0.00875

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00758

Hom.:

Bravo

AF:

0.00604

Asia WGS

AF:

0.00116

AC:

AN:

3468

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 06, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.6

DANN

Benign

0.80

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