rs11358611

chr12-88114389-GA-Gchr12-88114389-GA-GAA

Variant summary

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

The NM_025114.4(CEP290):c.2052+30del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00754 in 1,516,706 control chromosomes in the GnomAD database, including 673 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (368 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (305 hom.)
• Consequence: CEP290 NM_025114.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.661

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 12-88114389-GA-G is Benign according to our data. Variant chr12-88114389-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 261833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-88114389-GA-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP290	NM_025114.4	c.2052+30del		intron_variant		ENST00000552810.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP290	ENST00000552810.6	c.2052+30del		intron_variant		1	NM_025114.4	P4

Frequencies

GnomAD3 genomes AF: 0.0392 AC: 5962 AN: 151968 Hom.: 368 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000471

Gnomad OTH AF: 0.0321

GnomAD3 exomes AF: 0.00997 AC: 1392 AN: 139592 Hom.: 84 AF XY: 0.00811 AC XY: 597 AN XY: 73636

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.00690

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00152

Gnomad SAS exome AF: 0.00557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000374

Gnomad OTH exome AF: 0.00605

GnomAD4 exome AF: 0.00401 AC: 5469 AN: 1364620 Hom.: 305 Cov.: 26 AF XY: 0.00364 AC XY: 2454 AN XY: 673540

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.00874

Gnomad4 ASJ exome AF: 0.0000410

Gnomad4 EAS exome AF: 0.000879

Gnomad4 SAS exome AF: 0.00503

Gnomad4 FIN exome AF: 0.0000209

Gnomad4 NFE exome AF: 0.000158

Gnomad4 OTH exome AF: 0.00952

GnomAD4 genome AF: 0.0393 AC: 5974 AN: 152086 Hom.: 368 Cov.: 32 AF XY: 0.0379 AC XY: 2821 AN XY: 74386

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0158

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000471

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0217 Hom.: 37

Bravo AF: 0.0458

Asia WGS AF: 0.0100 AC: 35 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 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. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11358611; hg19: chr12-88508166;