rs184044181

Positions:

• chr12-88054300-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_025114.4(CEP290):​c.7034+40T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 1,277,926 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (9 hom.)
• Consequence: CEP290 NM_025114.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.348

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-88054300-A-T is Benign according to our data. Variant chr12-88054300-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 261854.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP290	NM_025114.4	c.7034+40T>A		intron_variant		ENST00000552810.6	NP_079390.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP290	ENST00000552810.6	c.7034+40T>A		intron_variant		1	NM_025114.4	ENSP00000448012.1

Frequencies

GnomAD3 genomes AF: 0.00235 AC: 356 AN: 151320 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000755

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.00191

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00291

Gnomad FIN AF: 0.000383

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00388

Gnomad OTH AF: 0.00337

GnomAD3 exomes AF: 0.00245 AC: 449 AN: 182950 Hom.: 1 AF XY: 0.00244 AC XY: 246 AN XY: 100874

Gnomad AFR exome AF: 0.000407

Gnomad AMR exome AF: 0.00182

Gnomad ASJ exome AF: 0.000415

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00246

Gnomad FIN exome AF: 0.000107

Gnomad NFE exome AF: 0.00387

Gnomad OTH exome AF: 0.00303

GnomAD4 exome AF: 0.00339 AC: 3823 AN: 1126496 Hom.: 9 Cov.: 16 AF XY: 0.00347 AC XY: 1984 AN XY: 571202

Gnomad4 AFR exome AF: 0.000795

Gnomad4 AMR exome AF: 0.00181

Gnomad4 ASJ exome AF: 0.000825

Gnomad4 EAS exome AF: 0.0000279

Gnomad4 SAS exome AF: 0.00248

Gnomad4 FIN exome AF: 0.000178

Gnomad4 NFE exome AF: 0.00404

Gnomad4 OTH exome AF: 0.00264

GnomAD4 genome AF: 0.00235 AC: 356 AN: 151430 Hom.: 1 Cov.: 32 AF XY: 0.00218 AC XY: 161 AN XY: 73984

Gnomad4 AFR AF: 0.000753

Gnomad4 AMR AF: 0.00191

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00291

Gnomad4 FIN AF: 0.000383

Gnomad4 NFE AF: 0.00388

Gnomad4 OTH AF: 0.00334

Alfa AF: 0.00276 Hom.: 1

Bravo AF: 0.00218

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.47
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs184044181; hg19: chr12-88448077;