5-37245833-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001384732.1(CPLANE1):c.94G>A(p.Val32Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00529 in 1,510,238 control chromosomes in the GnomAD database, including 394 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 0.028 ( 220 hom., cov: 30)

Exomes 𝑓: 0.0027 ( 174 hom. )

Consequence

CPLANE1
NM_001384732.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.56

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=0.0016393065).

BP6

Variant 5-37245833-C-T is Benign according to our data. Variant chr5-37245833-C-T is described in ClinVar as [Benign]. Clinvar id is 158062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPLANE1	NM_001384732.1 link	c.94G>A	p.Val32Ile	missense_variant	Exon 3 of 53	ENST00000651892.2	NP_001371661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CPLANE1	ENST00000651892.2 link	c.94G>A	p.Val32Ile	missense_variant	Exon 3 of 53		NM_001384732.1	ENSP00000498265.2	A0A494BZW6
CPLANE1	ENST00000508244.5 link	c.94G>A	p.Val32Ile	missense_variant	Exon 2 of 51	5		ENSP00000421690.1	Q9H799-1
CPLANE1	ENST00000675547.1 link	n.521-235G>A		intron_variant	Intron 1 of 14
CPLANE1	ENST00000425232.7 link	n.-237G>A		upstream_gene_variant		5		ENSP00000389014.3	A0A7I2XYG4

Frequencies

GnomAD3 genomes

AF:

0.0284

AC:

4318

AN:

151952

Hom.:

220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0983

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0123

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.00651

AC:

826

AN:

126950

Hom.:

AF XY:

0.00479

AC XY:

323

AN XY:

67416

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.00511

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000113

Gnomad SAS exome

AF:

0.000317

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.00203

GnomAD4 exome

AF:

0.00270

AC:

3671

AN:

1358168

Hom.:

174

Cov.:

AF XY:

0.00233

AC XY:

1554

AN XY:

668288

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.00591

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000287

Gnomad4 SAS exome

AF:

0.000288

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000545

Gnomad4 OTH exome

AF:

0.00623

GnomAD4 genome

AF:

0.0284

AC:

4324

AN:

152070

Hom.:

220

Cov.:

AF XY:

0.0273

AC XY:

2031

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0982

Gnomad4 AMR

AF:

0.0123

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.00356

Hom.:

Bravo

AF:

0.0335

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.105

AC:

145

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0102

AC:

237

Asia WGS

AF:

0.00549

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Oct 19, 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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Joubert syndrome 17

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0090

T;T

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.72

.;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.2

PROVEAN

Benign

-0.33

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.017

D;D

Sift4G

Benign

0.089

T;T

Vest4

0.14

MPC

0.26

ClinPred

0.022

GERP RS

4.3

Varity_R

0.098

gMVP

0.043

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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