12-88089495-TAA-TA

Position:

• chr12-88089495-TAA-TA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000552810.6(CEP290):​c.3574-9del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (59932 hom., cov: 0)
  • Exomes 𝑓: 0.94 (552196 hom.)
• Consequence: CEP290 ENST00000552810.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: 0.208

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 12-88089495-TA-T is Benign according to our data. Variant chr12-88089495-TA-T is described in ClinVar as [Benign]. Clinvar id is 96170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-88089495-TA-T is described in Lovd as [Benign].
• 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	c.3574-9del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000552810.6	NP_079390.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP290	ENST00000552810.6	c.3574-9del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_025114.4	ENSP00000448012	P4

Frequencies

GnomAD3 genomes AF: 0.882 AC: 133923 AN: 151880 Hom.: 59916 Cov.: 0

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.948

Gnomad OTH AF: 0.893

GnomAD3 exomes AF: 0.931 AC: 76331 AN: 82002 Hom.: 35734 AF XY: 0.932 AC XY: 40011 AN XY: 42938

Gnomad AFR exome AF: 0.705

Gnomad AMR exome AF: 0.939

Gnomad ASJ exome AF: 0.913

Gnomad EAS exome AF: 0.990

Gnomad SAS exome AF: 0.894

Gnomad FIN exome AF: 0.987

Gnomad NFE exome AF: 0.950

Gnomad OTH exome AF: 0.929

GnomAD4 exome AF: 0.942 AC: 1170044 AN: 1242604 Hom.: 552196 Cov.: 0 AF XY: 0.941 AC XY: 565434 AN XY: 600924

Gnomad4 AFR exome AF: 0.708

Gnomad4 AMR exome AF: 0.939

Gnomad4 ASJ exome AF: 0.906

Gnomad4 EAS exome AF: 0.993

Gnomad4 SAS exome AF: 0.898

Gnomad4 FIN exome AF: 0.984

Gnomad4 NFE exome AF: 0.949

Gnomad4 OTH exome AF: 0.925

GnomAD4 genome AF: 0.881 AC: 133981 AN: 151998 Hom.: 59932 Cov.: 0 AF XY: 0.885 AC XY: 65778 AN XY: 74286

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.919

Gnomad4 ASJ AF: 0.896

Gnomad4 EAS AF: 0.988

Gnomad4 SAS AF: 0.902

Gnomad4 FIN AF: 0.988

Gnomad4 NFE AF: 0.947

Gnomad4 OTH AF: 0.894

Alfa AF: 0.914 Hom.: 3709

Bravo AF: 0.869

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 20, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Leber congenital amaurosis Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

Senior-Loken syndrome 6 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 11, 2018

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. -

Bardet-Biedl syndrome 14 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis;C0687120:Nephronophthisis Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Meckel-Gruber syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Meckel syndrome, type 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Renal dysplasia and retinal aplasia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Familial aplasia of the vermis Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Bardet-Biedl syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Joubert syndrome 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs10717563; hg19: chr12-88483272;