rs16903511

chr5-37121664-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001384732.1(CPLANE1):c.9138C>G(p.Pro3046=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,614,124 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (66 hom.)
• Consequence: CPLANE1 NM_001384732.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.119

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=-0.84).
• BP6: Variant 5-37121664-G-C is Benign according to our data. Variant chr5-37121664-G-C is described in ClinVar as [Benign]. Clinvar id is 158059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00383 (584/152296) while in subpopulation AMR AF= 0.028 (428/15292). AF 95% confidence interval is 0.0258. There are 12 homozygotes in gnomad4. There are 304 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPLANE1	NM_001384732.1	c.9138C>G	p.Pro3046=	synonymous_variant	49/53	ENST00000651892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPLANE1	ENST00000651892.2	c.9138C>G	p.Pro3046=	synonymous_variant	49/53		NM_001384732.1	A2

Frequencies

GnomAD3 genomes AF: 0.00385 AC: 586 AN: 152178 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0222

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00573

GnomAD3 exomes AF: 0.00819 AC: 2060 AN: 251432 Hom.: 43 AF XY: 0.00661 AC XY: 898 AN XY: 135900

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.0477

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0190

Gnomad SAS exome AF: 0.000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00472

GnomAD4 exome AF: 0.00208 AC: 3041 AN: 1461828 Hom.: 66 Cov.: 31 AF XY: 0.00190 AC XY: 1379 AN XY: 727218

Gnomad4 AFR exome AF: 0.000418

Gnomad4 AMR exome AF: 0.0456

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0199

Gnomad4 SAS exome AF: 0.000800

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.00195

GnomAD4 genome AF: 0.00383 AC: 584 AN: 152296 Hom.: 12 Cov.: 32 AF XY: 0.00408 AC XY: 304 AN XY: 74482

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.0280

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0222

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.000974 Hom.: 0

Bravo AF: 0.00651

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Sep 23, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 29, 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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 21, 2014	- -

Orofaciodigital syndrome type 6;C3553264:Joubert syndrome 17 Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 28, 2021

- -

Joubert syndrome 17 Benign:1

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 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 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.79
Dann	Benign	0.36

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: rs16903511; hg19: chr5-37121766; COSMIC: COSV57061534; COSMIC: COSV57061534;