rs77014998

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001384732.1(CPLANE1):c.8344C>A(p.Pro2782Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,612,882 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 7 hom., cov: 32)

Exomes 𝑓: 0.011 ( 108 hom. )

Consequence

CPLANE1
NM_001384732.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.324

Publications

6 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=0.002856642).

BP6

Variant 5-37153769-G-T is Benign according to our data. Variant chr5-37153769-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 158055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0069 (1049/151962) while in subpopulation NFE AF = 0.0111 (752/67960). AF 95% confidence interval is 0.0104. There are 7 homozygotes in GnomAd4. There are 500 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPLANE1	NM_001384732.1 link	c.8344C>A	p.Pro2782Thr	missense_variant	Exon 42 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.8344C>A	p.Pro2782Thr	missense_variant	Exon 42 of 53		NM_001384732.1	ENSP00000498265.2

Frequencies

GnomAD3 genomes

AF:

0.00691

AC:

1049

AN:

151844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00439

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000835

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00662

AC:

1661

AN:

250998

AF XY:

0.00663

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00415

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00903

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00767

GnomAD4 exome

AF:

0.0109

AC:

15963

AN:

1460920

Hom.:

108

Cov.:

AF XY:

0.0105

AC XY:

7604

AN XY:

726666

show subpopulations

African (AFR)

AF:

0.00176

AC:

AN:

33466

American (AMR)

AF:

0.00468

AC:

209

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00103

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.000951

AC:

AN:

86194

European-Finnish (FIN)

AF:

0.00826

AC:

441

AN:

53380

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0132

AC:

14672

AN:

1111286

Other (OTH)

AF:

0.00774

AC:

467

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

769

1539

2308

3078

3847

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

582

1164

1746

2328

2910

<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:

0.00690

AC:

1049

AN:

151962

Hom.:

Cov.:

AF XY:

0.00673

AC XY:

500

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.00244

AC:

101

AN:

41418

American (AMR)

AF:

0.00439

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00105

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.0104

AC:

110

AN:

10572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0111

AC:

752

AN:

67960

Other (OTH)

AF:

0.00379

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

114

171

228

285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00958

Hom.:

Bravo

AF:

0.00623

TwinsUK

AF:

0.0156

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.00454

AC:

ESP6500EA

AF:

0.0115

AC:

ExAC

AF:

0.00655

AC:

795

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0107

EpiControl

AF:

0.0104

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jul 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CPLANE1: BP4, BS1, BS2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 03, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 25905921)

Joubert syndrome 17

Benign:3

Sep 21, 2015

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

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Apr 04, 2014

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Orofaciodigital syndrome type 6;C3553264:Joubert syndrome 17

Benign:1

Sep 14, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.9

(source)

DANN

Benign

0.097

DEOGEN2

Benign

0.0031

T;T;T

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.0

.;T;T

MetaRNN

Benign

0.0029

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;.;.

PhyloP100

0.32

PROVEAN

Benign

1.2

N;N;N

REVEL

Benign

0.037

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.42

T;T;T

Vest4

0.092

ClinPred

0.00055

GERP RS

2.3

Varity_R

0.025

gMVP

0.14

Mutation Taster

=98/2

polymorphism

(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

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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