dbSNP rs368215443: CEP290:c.5013-21A>G (chr12-88080416-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_025114.4(CEP290):c.5013-21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,539,108 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 3 hom. )

Consequence

CEP290
NM_025114.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.197

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:

LOC124902977 (HGNC:):

LOC124902977 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 12-88080416-T-C is Benign according to our data. Variant chr12-88080416-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 261848.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP290	NM_025114.4 link	c.5013-21A>G		intron_variant	Intron 37 of 53	ENST00000552810.6	NP_079390.3	O15078Q05BJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP290	ENST00000552810.6 link	c.5013-21A>G		intron_variant	Intron 37 of 53	1	NM_025114.4	ENSP00000448012.1		O15078

Frequencies

GnomAD3 genomes

AF:

0.000645

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00112

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000887

AC:

199

AN:

224310

Hom.:

AF XY:

0.000886

AC XY:

108

AN XY:

121932

show subpopulations

Gnomad AFR exome

AF:

0.000136

Gnomad AMR exome

AF:

0.000177

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.00146

Gnomad NFE exome

AF:

0.00115

Gnomad OTH exome

AF:

0.000380

GnomAD4 exome

AF:

0.00113

AC:

1562

AN:

1387078

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

803

AN XY:

689174

show subpopulations

Gnomad4 AFR exome

AF:

0.000130

Gnomad4 AMR exome

AF:

0.000131

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00169

Gnomad4 FIN exome

AF:

0.00128

Gnomad4 NFE exome

AF:

0.00122

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.000645

AC:

AN:

152030

Hom.:

Cov.:

AF XY:

0.000606

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00112

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000898

Hom.:

Bravo

AF:

0.000521

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.1

DANN

Benign

0.61

La Branchor

0.47

BranchPoint Hunter

3.0

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