rs7973969

chr12-88077204-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_025114.4(CEP290):c.5709+18C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00894 in 1,597,158 control chromosomes in the GnomAD database, including 1,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (633 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (541 hom.)
• Consequence: CEP290 NM_025114.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.344

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]

LOC124902977 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 12-88077204-G-T is Benign according to our data. Variant chr12-88077204-G-T is described in ClinVar as [Benign]. Clinvar id is 126263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-88077204-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP290	NM_025114.4	c.5709+18C>A		intron_variant		ENST00000552810.6
LOC124902977	XR_007063393.1	n.887-5109G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP290	ENST00000552810.6	c.5709+18C>A		intron_variant		1	NM_025114.4	P4

Frequencies

GnomAD3 genomes AF: 0.0494 AC: 7503 AN: 151888 Hom.: 632 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000339

Gnomad OTH AF: 0.0292

GnomAD3 exomes AF: 0.0120 AC: 2841 AN: 236888 Hom.: 233 AF XY: 0.00891 AC XY: 1146 AN XY: 128576

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.00639

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000360

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000147

Gnomad OTH exome AF: 0.00534

GnomAD4 exome AF: 0.00468 AC: 6760 AN: 1445152 Hom.: 541 Cov.: 30 AF XY: 0.00404 AC XY: 2900 AN XY: 718360

Gnomad4 AFR exome AF: 0.175

Gnomad4 AMR exome AF: 0.00812

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000424

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000732

Gnomad4 OTH exome AF: 0.0100

GnomAD4 genome AF: 0.0494 AC: 7515 AN: 152006 Hom.: 633 Cov.: 32 AF XY: 0.0476 AC XY: 3534 AN XY: 74318

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.0199

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000339

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0237 Hom.: 42

Bravo AF: 0.0560

Asia WGS AF: 0.00751 AC: 26 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 27, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 30, 2014	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. -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.1
Dann	Benign	0.28

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: rs7973969; hg19: chr12-88470981;