rs10076911

Variant names:

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.6098T>G(p.Phe2033Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,758 control chromosomes in the GnomAD database, including 12,862 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 Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2836 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10026 hom. )

Consequence

CPLANE1
NM_001384732.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.864

Publications

24 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=0.0032223165).

BP6

Variant 5-37173828-A-C is Benign according to our data. Variant chr5-37173828-A-C is described in ClinVar as Benign. ClinVar VariationId is 158048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPLANE1	NM_001384732.1 link	c.6098T>G	p.Phe2033Cys	missense_variant	Exon 32 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.6098T>G	p.Phe2033Cys	missense_variant	Exon 32 of 53		NM_001384732.1	ENSP00000498265.2		A0A494BZW6

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25915

AN:

152028

Hom.:

2825

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.0806

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.172

GnomAD2 exomes

AF:

0.134

AC:

33738

AN:

251414

AF XY:

0.127

show subpopulations

Gnomad AFR exome

AF:

0.311

Gnomad AMR exome

AF:

0.188

Gnomad ASJ exome

AF:

0.166

Gnomad EAS exome

AF:

0.0786

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.110

AC:

161387

AN:

1461614

Hom.:

10026

Cov.:

AF XY:

0.110

AC XY:

79701

AN XY:

727128

show subpopulations

African (AFR)

AF:

0.314

AC:

10514

AN:

33456

American (AMR)

AF:

0.184

AC:

8233

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

4287

AN:

26136

East Asian (EAS)

AF:

0.0570

AC:

2261

AN:

39696

South Asian (SAS)

AF:

0.102

AC:

8828

AN:

86250

European-Finnish (FIN)

AF:

0.129

AC:

6868

AN:

53412

Middle Eastern (MID)

AF:

0.138

AC:

798

AN:

5766

European-Non Finnish (NFE)

AF:

0.101

AC:

112106

AN:

1111796

Other (OTH)

AF:

0.124

AC:

7492

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

7089

14178

21266

28355

35444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4212

8424

12636

16848

21060

<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:

0.171

AC:

25978

AN:

152144

Hom.:

2836

Cov.:

AF XY:

0.172

AC XY:

12761

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.311

AC:

12891

AN:

41458

American (AMR)

AF:

0.173

AC:

2651

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

518

AN:

3466

East Asian (EAS)

AF:

0.0802

AC:

415

AN:

5176

South Asian (SAS)

AF:

0.108

AC:

522

AN:

4820

European-Finnish (FIN)

AF:

0.134

AC:

1426

AN:

10608

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.105

AC:

7123

AN:

68006

Other (OTH)

AF:

0.174

AC:

368

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1029

2058

3088

4117

5146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

264

528

792

1056

1320

<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:

0.130

Hom.:

5797

Bravo

AF:

0.178

TwinsUK

AF:

0.0998

AC:

370

ALSPAC

AF:

0.0877

AC:

338

ESP6500AA

AF:

0.302

AC:

1329

ESP6500EA

AF:

0.111

AC:

957

ExAC

AF:

0.135

AC:

16398

Asia WGS

AF:

0.155

AC:

537

AN:

3478

EpiCase

AF:

0.117

EpiControl

AF:

0.115

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

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 13, 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. -

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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.0

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.0046

T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.086

.;T;T

MetaRNN

Benign

0.0032

T;T;T

MetaSVM

Benign

-0.91

PhyloP100

0.86

PROVEAN

Benign

1.4

N;N;N

REVEL

Benign

0.046

Sift

Benign

0.19

T;T;T

Sift4G

Benign

0.18

T;T;T

Vest4

0.020

MPC

0.17

ClinPred

0.00059

GERP RS

3.8

Varity_R

0.056

gMVP

0.21

Mutation Taster

=100/0

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

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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