5-37106961-G-A

Position:

• chr5-37106961-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001384732.1(CPLANE1):​c.*641C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00614 in 985,276 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (58 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (30 hom.)
• Consequence: CPLANE1 NM_001384732.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0820

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-37106961-G-A is Benign according to our data. Variant chr5-37106961-G-A is described in ClinVar as [Benign]. Clinvar id is 353406.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPLANE1	NM_001384732.1	c.*641C>T		3_prime_UTR_variant	53/53	ENST00000651892.2	NP_001371661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPLANE1	ENST00000651892	c.*641C>T		3_prime_UTR_variant	53/53		NM_001384732.1	ENSP00000498265.2

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2615 AN: 152060 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00819

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00331

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.00412 AC: 3429 AN: 833098 Hom.: 30 Cov.: 30 AF XY: 0.00413 AC XY: 1590 AN XY: 384714

Gnomad4 AFR exome AF: 0.0583

Gnomad4 AMR exome AF: 0.00304

Gnomad4 ASJ exome AF: 0.000194

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0106

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00278

Gnomad4 OTH exome AF: 0.00670

GnomAD4 genome AF: 0.0172 AC: 2619 AN: 152178 Hom.: 58 Cov.: 32 AF XY: 0.0169 AC XY: 1259 AN XY: 74422

Gnomad4 AFR AF: 0.0524

Gnomad4 AMR AF: 0.00818

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00995

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00331

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00884 Hom.: 2

Bravo AF: 0.0198

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.90
CADD	Benign	3.0
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: rs116744214; hg19: chr5-37107063;