chr5-37195926-C-T

Position:

chr5-37195926-C-T

Variant summary

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

The NM_001384732.1(CPLANE1):c.3743G>A(p.Gly1248Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0363 in 1,612,448 control chromosomes in the GnomAD database, including 1,295 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 91 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1204 hom. )

Consequence

CPLANE1
NM_001384732.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.00

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=0.0024533272).

BP6

Variant 5-37195926-C-T is Benign according to our data. Variant chr5-37195926-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 158031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-37195926-C-T is described in Lovd as [Benign]. Variant chr5-37195926-C-T is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0823 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.3743G>A	p.Gly1248Asp	missense_variant	21/53	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.3743G>A	p.Gly1248Asp	missense_variant	21/53		NM_001384732.1	ENSP00000498265	A2

Frequencies

GnomAD3 genomes

AF:

0.0282

AC:

4290

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00765

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0311

Gnomad ASJ

AF:

0.0865

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0394

Gnomad FIN

AF:

0.0232

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0386

Gnomad OTH

AF:

0.0364

GnomAD3 exomes

AF:

0.0303

AC:

7593

AN:

250198

Hom.:

157

AF XY:

0.0316

AC XY:

4276

AN XY:

135266

show subpopulations

Gnomad AFR exome

AF:

0.00728

Gnomad AMR exome

AF:

0.0231

Gnomad ASJ exome

AF:

0.0739

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0332

Gnomad FIN exome

AF:

0.0220

Gnomad NFE exome

AF:

0.0372

Gnomad OTH exome

AF:

0.0408

GnomAD4 exome

AF:

0.0371

AC:

54241

AN:

1460218

Hom.:

1204

Cov.:

AF XY:

0.0371

AC XY:

26922

AN XY:

726416

show subpopulations

Gnomad4 AFR exome

AF:

0.00769

Gnomad4 AMR exome

AF:

0.0240

Gnomad4 ASJ exome

AF:

0.0746

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.0329

Gnomad4 FIN exome

AF:

0.0224

Gnomad4 NFE exome

AF:

0.0397

Gnomad4 OTH exome

AF:

0.0384

GnomAD4 genome

AF:

0.0282

AC:

4290

AN:

152230

Hom.:

Cov.:

AF XY:

0.0276

AC XY:

2051

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00763

Gnomad4 AMR

AF:

0.0310

Gnomad4 ASJ

AF:

0.0865

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0394

Gnomad4 FIN

AF:

0.0232

Gnomad4 NFE

AF:

0.0386

Gnomad4 OTH

AF:

0.0365

Alfa

AF:

0.0372

Hom.:

197

Bravo

AF:

0.0272

TwinsUK

AF:

0.0402

AC:

149

ALSPAC

AF:

0.0415

AC:

160

ESP6500AA

AF:

0.00885

AC:

ESP6500EA

AF:

0.0429

AC:

369

ExAC

AF:

0.0302

AC:

3673

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0410

EpiControl

AF:

0.0452

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

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 22, 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:2

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. -
Likely benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -

not provided

Benign:2

Likely 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

0.15

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.021

T;T;T

Eigen

Benign

0.19

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.58

.;T;T

MetaRNN

Benign

0.0025

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.52

D;N;N

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.23

T;T;T

Vest4

0.18

MPC

0.33

ClinPred

0.014

GERP RS

5.2

Varity_R

0.10

gMVP

0.13

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