rs10805625

Variant names:

• chr5-37175989-A-G
• rs10805625
• ENST00000511781.1:n.111T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000511781.1(CPLANE1):​n.111T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,598,720 control chromosomes in the GnomAD database, including 10,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1951 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8885 hom.)
• Consequence: CPLANE1 ENST00000511781.1 non_coding_transcript_exon
• Scores: Splicing: ADA: 0.00001170
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.723
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• Joubert syndrome 17

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, ClinGen, G2P, Illumina, Labcorp Genetics (formerly Invitae)
• orofaciodigital syndrome type 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-37175989-A-G is Benign according to our data. Variant chr5-37175989-A-G is described in ClinVar as Benign. ClinVar VariationId is 158046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPLANE1	NM_001384732.1	c.5901-3T>C		splice_region_variant, intron_variant	Intron 30 of 52	ENST00000651892.2	NP_001371661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPLANE1	ENST00000651892.2	c.5901-3T>C		splice_region_variant, intron_variant	Intron 30 of 52		NM_001384732.1	ENSP00000498265.2

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22379 AN: 152030 Hom.: 1951 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0546

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.156

GnomAD2 exomes AF: 0.124 AC: 31046 AN: 250658 AF XY: 0.119

Gnomad AFR exome AF: 0.233

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.166

Gnomad EAS exome AF: 0.0512

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.106 AC: 153643 AN: 1446572 Hom.: 8885 Cov.: 26 AF XY: 0.106 AC XY: 76231 AN XY: 720682

African (AFR) AF: 0.235 AC: 7756 AN: 33042

American (AMR) AF: 0.164 AC: 7300 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 4255 AN: 26024

East Asian (EAS) AF: 0.0359 AC: 1421 AN: 39568

South Asian (SAS) AF: 0.0996 AC: 8541 AN: 85766

European-Finnish (FIN) AF: 0.129 AC: 6852 AN: 53298

Middle Eastern (MID) AF: 0.133 AC: 755 AN: 5660

European-Non Finnish (NFE) AF: 0.0999 AC: 109773 AN: 1098778

Other (OTH) AF: 0.117 AC: 6990 AN: 59844

GnomAD4 genome AF: 0.147 AC: 22405 AN: 152148 Hom.: 1951 Cov.: 32 AF XY: 0.149 AC XY: 11069 AN XY: 74394

African (AFR) AF: 0.234 AC: 9715 AN: 41474

American (AMR) AF: 0.161 AC: 2460 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3468

East Asian (EAS) AF: 0.0541 AC: 281 AN: 5190

South Asian (SAS) AF: 0.105 AC: 506 AN: 4824

European-Finnish (FIN) AF: 0.134 AC: 1424 AN: 10590

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7105 AN: 68002

Other (OTH) AF: 0.158 AC: 333 AN: 2112

Alfa AF: 0.130 Hom.: 692

Bravo AF: 0.151

Asia WGS AF: 0.139 AC: 481 AN: 3476

EpiCase AF: 0.117

EpiControl AF: 0.115

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 14, 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. -

Joubert syndrome 17 Benign:3

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 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. -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

Feb 03, 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.63
DANN	Benign	0.34
PhyloP100		-0.72
Mutation Taster		=85/15	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000012
dbscSNV1_RF	Benign	0.020
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

Other links and lift over

dbSNP: rs10805625; hg19: chr5-37176091; COSMIC: COSV57071349;