rs111508546

Positions:

• chr5-37185087-GAA-G
• chr5-37185087-GAA-GA
• chr5-37185087-GAA-GAAAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001384732.1(CPLANE1):​c.4190-10_4190-9delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00659 in 1,588,058 control chromosomes in the GnomAD database, including 611 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (335 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (276 hom.)
• Consequence: CPLANE1 NM_001384732.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.774

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 -16 ACMG points.

• BP6: Variant 5-37185087-GAA-G is Benign according to our data. Variant chr5-37185087-GAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 195905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-37185087-GAA-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPLANE1	NM_001384732.1	c.4190-10_4190-9delTT		intron_variant		ENST00000651892.2	NP_001371661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPLANE1	ENST00000651892.2	c.4190-10_4190-9delTT		intron_variant			NM_001384732.1	ENSP00000498265.2

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5469 AN: 152092 Hom.: 335 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0287

GnomAD3 exomes AF: 0.00938 AC: 2094 AN: 223192 Hom.: 120 AF XY: 0.00678 AC XY: 822 AN XY: 121234

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.00588

Gnomad ASJ exome AF: 0.000382

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000160

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.00386

GnomAD4 exome AF: 0.00347 AC: 4984 AN: 1435848 Hom.: 276 AF XY: 0.00297 AC XY: 2121 AN XY: 713484

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.00638

Gnomad4 ASJ exome AF: 0.000204

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000196

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000165

Gnomad4 OTH exome AF: 0.00760

GnomAD4 genome AF: 0.0360 AC: 5476 AN: 152210 Hom.: 335 Cov.: 32 AF XY: 0.0344 AC XY: 2561 AN XY: 74424

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0140

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0180 Hom.: 15

Bravo AF: 0.0401

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 02, 2014	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2018	- -

Familial aplasia of the vermis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs111508546; hg19: chr5-37185189;