rs13356183

Positions:

• chr5-37226858-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001384732.1(CPLANE1):​c.1737G>A​(p.Ala579Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,551,234 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (44 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (64 hom.)
• Consequence: CPLANE1 NM_001384732.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.693

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=-0.67).
• BP6: Variant 5-37226858-C-T is Benign according to our data. Variant chr5-37226858-C-T is described in ClinVar as [Benign]. Clinvar id is 158027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.693 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPLANE1	NM_001384732.1	c.1737G>A	p.Ala579Ala	synonymous_variant	12/53	ENST00000651892.2	NP_001371661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPLANE1	ENST00000651892.2	c.1737G>A	p.Ala579Ala	synonymous_variant	12/53		NM_001384732.1	ENSP00000498265.2

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 2005 AN: 152110 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.0453

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.00910

GnomAD3 exomes AF: 0.00315 AC: 493 AN: 156314 Hom.: 16 AF XY: 0.00242 AC XY: 200 AN XY: 82696

Gnomad AFR exome AF: 0.0487

Gnomad AMR exome AF: 0.00281

Gnomad ASJ exome AF: 0.000118

Gnomad EAS exome AF: 0.0000918

Gnomad SAS exome AF: 0.000176

Gnomad FIN exome AF: 0.0000592

Gnomad NFE exome AF: 0.000298

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00161 AC: 2247 AN: 1399006 Hom.: 64 Cov.: 32 AF XY: 0.00143 AC XY: 988 AN XY: 689928

Gnomad4 AFR exome AF: 0.0531

Gnomad4 AMR exome AF: 0.00280

Gnomad4 ASJ exome AF: 0.000278

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.000316

Gnomad4 FIN exome AF: 0.0000407

Gnomad4 NFE exome AF: 0.000187

Gnomad4 OTH exome AF: 0.00365

GnomAD4 genome AF: 0.0133 AC: 2022 AN: 152228 Hom.: 44 Cov.: 32 AF XY: 0.0135 AC XY: 1002 AN XY: 74418

Gnomad4 AFR AF: 0.0455

Gnomad4 AMR AF: 0.00516

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00504 Hom.: 6

Bravo AF: 0.0153

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 03, 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. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Joubert syndrome 17 Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.5
DANN	Benign	0.43

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: rs13356183; hg19: chr5-37226960;