rs587783350

chr5-37177614-C-Achr5-37177614-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001384732.1(CPLANE1):c.5900+7G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00598 in 1,608,220 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (61 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (76 hom.)
• Consequence: CPLANE1 NM_001384732.1 splice_region, intron
• Scores: Splicing: ADA: 0.00001557
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.536

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-37177614-C-A is Benign according to our data. Variant chr5-37177614-C-A is described in ClinVar as [Benign]. Clinvar id is 158045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-37177614-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPLANE1	NM_001384732.1	c.5900+7G>T		splice_region_variant, intron_variant		ENST00000651892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPLANE1	ENST00000651892.2	c.5900+7G>T		splice_region_variant, intron_variant			NM_001384732.1	A2

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2631 AN: 152048 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0527

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.00337

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.00735 AC: 1838 AN: 250132 Hom.: 32 AF XY: 0.00705 AC XY: 953 AN XY: 135224

Gnomad AFR exome AF: 0.0546

Gnomad AMR exome AF: 0.00540

Gnomad ASJ exome AF: 0.000499

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00895

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.00401

Gnomad OTH exome AF: 0.00574

GnomAD4 exome AF: 0.00479 AC: 6978 AN: 1456054 Hom.: 76 Cov.: 28 AF XY: 0.00498 AC XY: 3611 AN XY: 724702

Gnomad4 AFR exome AF: 0.0559

Gnomad4 AMR exome AF: 0.00573

Gnomad4 ASJ exome AF: 0.000422

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0101

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.00309

Gnomad4 OTH exome AF: 0.00721

GnomAD4 genome AF: 0.0173 AC: 2635 AN: 152166 Hom.: 61 Cov.: 32 AF XY: 0.0169 AC XY: 1261 AN XY: 74404

Gnomad4 AFR AF: 0.0526

Gnomad4 AMR AF: 0.00804

Gnomad4 ASJ AF: 0.000866

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00996

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00337

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.00735 Hom.: 6

Bravo AF: 0.0198

EpiCase AF: 0.00382

EpiControl AF: 0.00658

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 23, 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: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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.2
Dann	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0060
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: rs78315844; hg19: chr5-37177716;