rs75589774

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001384732.1(CPLANE1):c.5381C>T(p.Pro1794Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,612,254 control chromosomes in the GnomAD database, including 8,822 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 895 hom., cov: 32)

Exomes 𝑓: 0.10 ( 7927 hom. )

Consequence

CPLANE1
NM_001384732.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.98

Publications

23 publications found

Variant links:

Genes affected

CPLANE1 (HGNC:25801): (ciliogenesis and planar polarity effector complex subunit 1) The protein encoded by this gene has putative coiled-coil domains and may be a transmembrane protein. Defects in this gene are a cause of Joubert syndrome (JBTS). [provided by RefSeq, May 2012]

CPLANE1 Gene-Disease associations (from GenCC):

Joubert syndrome 17
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, ClinGen, G2P, Illumina, Labcorp Genetics (formerly Invitae)
orofaciodigital syndrome type 6
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
Joubert syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CPLANE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013924539).

BP6

Variant 5-37182800-G-A is Benign according to our data. Variant chr5-37182800-G-A is described in ClinVar as Benign. ClinVar VariationId is 158040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPLANE1	NM_001384732.1 link	c.5381C>T	p.Pro1794Leu	missense_variant	Exon 26 of 53	ENST00000651892.2	NP_001371661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPLANE1	ENST00000651892.2 link	c.5381C>T	p.Pro1794Leu	missense_variant	Exon 26 of 53		NM_001384732.1	ENSP00000498265.2

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15839

AN:

151986

Hom.:

895

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0875

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.0543

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.121

GnomAD2 exomes

AF:

0.111

AC:

27809

AN:

250072

AF XY:

0.110

show subpopulations

Gnomad AFR exome

AF:

0.0829

Gnomad AMR exome

AF:

0.155

Gnomad ASJ exome

AF:

0.156

Gnomad EAS exome

AF:

0.0513

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.106

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.102

AC:

149101

AN:

1460152

Hom.:

7927

Cov.:

AF XY:

0.102

AC XY:

74304

AN XY:

726400

show subpopulations

African (AFR)

AF:

0.0849

AC:

2839

AN:

33420

American (AMR)

AF:

0.152

AC:

6770

AN:

44458

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

4063

AN:

26092

East Asian (EAS)

AF:

0.0361

AC:

1429

AN:

39628

South Asian (SAS)

AF:

0.0994

AC:

8559

AN:

86066

European-Finnish (FIN)

AF:

0.130

AC:

6918

AN:

53258

Middle Eastern (MID)

AF:

0.129

AC:

746

AN:

5762

European-Non Finnish (NFE)

AF:

0.100

AC:

111356

AN:

1111158

Other (OTH)

AF:

0.106

AC:

6421

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

6368

12735

19103

25470

31838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4060

8120

12180

16240

20300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.104

AC:

15858

AN:

152102

Hom.:

895

Cov.:

AF XY:

0.108

AC XY:

8005

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0876

AC:

3636

AN:

41498

American (AMR)

AF:

0.140

AC:

2136

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

487

AN:

3470

East Asian (EAS)

AF:

0.0537

AC:

278

AN:

5178

South Asian (SAS)

AF:

0.106

AC:

511

AN:

4822

European-Finnish (FIN)

AF:

0.136

AC:

1443

AN:

10580

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.104

AC:

7050

AN:

67972

Other (OTH)

AF:

0.124

AC:

260

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

732

1463

2195

2926

3658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.102

Hom.:

1955

Bravo

AF:

0.103

TwinsUK

AF:

0.0987

AC:

366

ALSPAC

AF:

0.0872

AC:

336

ESP6500AA

AF:

0.0828

AC:

365

ESP6500EA

AF:

0.109

AC:

941

ExAC

AF:

0.110

AC:

13324

Asia WGS

AF:

0.129

AC:

446

AN:

3478

EpiCase

AF:

0.116

EpiControl

AF:

0.113

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 14, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Joubert syndrome 17

Benign:3

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

T;T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.040

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.75

.;T;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-1.0

PhyloP100

3.0

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.095

Sift

Benign

0.86

T;T;T

Sift4G

Benign

0.86

T;T;T

Vest4

0.11

MPC

0.14

ClinPred

0.012

GERP RS

4.8

Varity_R

0.076

gMVP

0.22

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over