rs143312971

chr5-37183483-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001384732.1(CPLANE1):c.4698A>G(p.Leu1566=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00581 in 1,613,182 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (45 hom.)
• Consequence: CPLANE1 NM_001384732.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.221

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-37183483-T-C is Benign according to our data. Variant chr5-37183483-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 158037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-37183483-T-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.221 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00464 (707/152308) while in subpopulation NFE AF= 0.00776 (528/68024). AF 95% confidence interval is 0.00721. There are 1 homozygotes in gnomad4. There are 316 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPLANE1	NM_001384732.1	c.4698A>G	p.Leu1566=	synonymous_variant	26/53	ENST00000651892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPLANE1	ENST00000651892.2	c.4698A>G	p.Leu1566=	synonymous_variant	26/53		NM_001384732.1	A2

Frequencies

GnomAD3 genomes AF: 0.00465 AC: 707 AN: 152190 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00674

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00776

Gnomad OTH AF: 0.00480

GnomAD3 exomes AF: 0.00458 AC: 1148 AN: 250894 Hom.: 3 AF XY: 0.00467 AC XY: 633 AN XY: 135626

Gnomad AFR exome AF: 0.000802

Gnomad AMR exome AF: 0.00400

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.000653

Gnomad SAS exome AF: 0.000589

Gnomad FIN exome AF: 0.00106

Gnomad NFE exome AF: 0.00806

Gnomad OTH exome AF: 0.00458

GnomAD4 exome AF: 0.00593 AC: 8660 AN: 1460874 Hom.: 45 Cov.: 31 AF XY: 0.00582 AC XY: 4231 AN XY: 726798

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.00416

Gnomad4 ASJ exome AF: 0.000574

Gnomad4 EAS exome AF: 0.000177

Gnomad4 SAS exome AF: 0.000823

Gnomad4 FIN exome AF: 0.00135

Gnomad4 NFE exome AF: 0.00714

Gnomad4 OTH exome AF: 0.00533

GnomAD4 genome AF: 0.00464 AC: 707 AN: 152308 Hom.: 1 Cov.: 32 AF XY: 0.00424 AC XY: 316 AN XY: 74466

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.00673

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00776

Gnomad4 OTH AF: 0.00475

Alfa AF: 0.00637 Hom.: 1

Bravo AF: 0.00480

Asia WGS AF: 0.00116 AC: 4 AN: 3472

EpiCase AF: 0.00883

EpiControl AF: 0.00795

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:5

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 11, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	CPLANE1: BP4, BP7, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

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	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 14, 2015	- -

Joubert syndrome 17 Benign:2

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely 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	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.4
Dann	Benign	0.62

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

Other links and lift over

dbSNP: rs143312971; hg19: chr5-37183585;