rs75589774

Positions:

Variant summary

Our verdict is Benign. Variant got -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. 11/18 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 158040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-37182800-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
CPLANE1	NM_001384732.1 linkuse as main transcript	c.5381C>T	p.Pro1794Leu	missense_variant	26/53	ENST00000651892.2	NP_001371661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPLANE1	ENST00000651892.2 linkuse as main transcript	c.5381C>T	p.Pro1794Leu	missense_variant	26/53		NM_001384732.1	ENSP00000498265	A2

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

GnomAD3 exomes

AF:

0.111

AC:

27809

AN:

250072

Hom.:

1620

AF XY:

0.110

AC XY:

14828

AN XY:

135184

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 SAS exome

AF:

0.101

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

Gnomad4 AFR exome

AF:

0.0849

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.0361

Gnomad4 SAS exome

AF:

0.0994

Gnomad4 FIN exome

AF:

0.130

Gnomad4 NFE exome

AF:

0.100

Gnomad4 OTH exome

AF:

0.106

GnomAD4 genome

AF:

0.104

AC:

15858

AN:

152102

Hom.:

895

Cov.:

AF XY:

0.108

AC XY:

8005

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0876

Gnomad4 AMR

AF:

0.140

Gnomad4 ASJ

AF:

0.140

Gnomad4 EAS

AF:

0.0537

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.104

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.102

Hom.:

1404

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 14, 2016	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. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Joubert syndrome 17

Benign:3

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

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

MutationTaster

Benign

1.0

P;P;P

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

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