rs10076911

Positions:

chr5-37173828-A-C

Variant summary

Our verdict is Benign. Variant got -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. 12/18 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

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=0.0032223165).

BP6

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

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/exons	MANE	Protein	UniProt
CPLANE1	NM_001384732.1 linkuse as main transcript	c.6098T>G	p.Phe2033Cys	missense_variant	32/53	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.6098T>G	p.Phe2033Cys	missense_variant	32/53		NM_001384732.1	ENSP00000498265	A2

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

GnomAD3 exomes

AF:

0.134

AC:

33738

AN:

251414

Hom.:

2644

AF XY:

0.127

AC XY:

17286

AN XY:

135880

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 SAS exome

AF:

0.104

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

Gnomad4 AFR exome

AF:

0.314

Gnomad4 AMR exome

AF:

0.184

Gnomad4 ASJ exome

AF:

0.164

Gnomad4 EAS exome

AF:

0.0570

Gnomad4 SAS exome

AF:

0.102

Gnomad4 FIN exome

AF:

0.129

Gnomad4 NFE exome

AF:

0.101

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.171

AC:

25978

AN:

152144

Hom.:

2836

Cov.:

AF XY:

0.172

AC XY:

12761

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.311

Gnomad4 AMR

AF:

0.173

Gnomad4 ASJ

AF:

0.149

Gnomad4 EAS

AF:

0.0802

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.134

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.174

Alfa

AF:

0.119

Hom.:

3101

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

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
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. -
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, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

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

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

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

MutationTaster

Benign

1.0

P;P;P

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

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