rs114126795

Positions:

• chr5-37153827-G-A
• chr5-37153827-G-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.8286C>T​(p.Asp2762=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00767 in 1,614,050 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0079 (85 hom.)
• Consequence: CPLANE1 NM_001384732.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.298

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=-0.78).
• BP6: Variant 5-37153827-G-A is Benign according to our data. Variant chr5-37153827-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 158054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-37153827-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.298 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00575 (875/152240) while in subpopulation SAS AF= 0.0143 (69/4820). AF 95% confidence interval is 0.0116. There are 4 homozygotes in gnomad4. There are 456 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPLANE1	NM_001384732.1	c.8286C>T	p.Asp2762=	synonymous_variant	42/53	ENST00000651892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPLANE1	ENST00000651892.2	c.8286C>T	p.Asp2762=	synonymous_variant	42/53		NM_001384732.1	A2

Frequencies

GnomAD3 genomes AF: 0.00576 AC: 876 AN: 152122 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00717

Gnomad OTH AF: 0.00623

GnomAD3 exomes AF: 0.00636 AC: 1598 AN: 251326 Hom.: 20 AF XY: 0.00674 AC XY: 915 AN XY: 135820

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0129

Gnomad FIN exome AF: 0.0159

Gnomad NFE exome AF: 0.00639

Gnomad OTH exome AF: 0.00570

GnomAD4 exome AF: 0.00787 AC: 11511 AN: 1461810 Hom.: 85 Cov.: 31 AF XY: 0.00787 AC XY: 5722 AN XY: 727210

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.00177

Gnomad4 ASJ exome AF: 0.000918

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0134

Gnomad4 FIN exome AF: 0.0164

Gnomad4 NFE exome AF: 0.00796

Gnomad4 OTH exome AF: 0.00699

GnomAD4 genome AF: 0.00575 AC: 875 AN: 152240 Hom.: 4 Cov.: 32 AF XY: 0.00613 AC XY: 456 AN XY: 74436

Gnomad4 AFR AF: 0.00132

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0143

Gnomad4 FIN AF: 0.0183

Gnomad4 NFE AF: 0.00717

Gnomad4 OTH AF: 0.00617

Alfa AF: 0.00395 Hom.: 2

Bravo AF: 0.00417

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.00611

EpiControl AF: 0.00593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 09, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 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. -

Joubert syndrome 17 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Jun 28, 2017	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	CPLANE1: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.9
DANN	Benign	0.27

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: rs114126795; hg19: chr5-37153929; COSMIC: COSV57056523; COSMIC: COSV57056523;