rs144081297

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001384732.1(CPLANE1):c.9454G>A(p.Gly3152Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,614,176 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 4 hom. )

Consequence

CPLANE1
NM_001384732.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:6B:2

Conservation

PhyloP100: 0.0810

Publications

4 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, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Illumina
orofaciodigital syndrome type 6
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010336041).

BP6

Variant 5-37108418-C-T is Benign according to our data. Variant chr5-37108418-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 385186.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000867 (132/152326) while in subpopulation NFE AF = 0.00159 (108/68032). AF 95% confidence interval is 0.00134. There are 0 homozygotes in GnomAd4. There are 65 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384732.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	NM_001384732.1	MANE Select	c.9454G>A	p.Gly3152Arg	missense	Exon 52 of 53	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.9292G>A	p.Gly3098Arg	missense	Exon 51 of 52	NP_075561.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPLANE1	ENST00000651892.2	MANE Select	c.9454G>A	p.Gly3152Arg	missense	Exon 52 of 53	ENSP00000498265.2	A0A494BZW6
CPLANE1	ENST00000514429.5	TSL:1	c.6490G>A	p.Gly2164Arg	missense	Exon 36 of 37	ENSP00000424223.1	H0Y9I8
CPLANE1	ENST00000509849.5	TSL:1	n.*796G>A		non_coding_transcript_exon	Exon 36 of 37	ENSP00000426337.1	H0YA77

Frequencies

GnomAD3 genomes

AF:

0.000867

AC:

132

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000895

AC:

225

AN:

251334

AF XY:

0.000854

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00126

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00152

AC:

2215

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

1092

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33478

American (AMR)

AF:

0.00134

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000429

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0000749

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00181

AC:

2012

AN:

1111982

Other (OTH)

AF:

0.00147

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

110

219

329

438

548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<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:

0.000867

AC:

132

AN:

152326

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41570

American (AMR)

AF:

0.000523

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00159

AC:

108

AN:

68032

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00138

Hom.:

Bravo

AF:

0.000971

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000939

AC:

114

EpiCase

AF:

0.00131

EpiControl

AF:

0.00202

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

CPLANE1-related disorder (1)

Joubert syndrome 17 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.62

M_CAP

Benign

0.013

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.89

PhyloP100

0.081

PROVEAN

Benign

-1.0

REVEL

Benign

0.12

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.010

Vest4

0.17

MVP

0.48

MPC

0.30

ClinPred

0.014

GERP RS

3.4

Varity_R

0.094

gMVP

0.068

Mutation Taster

=96/4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over