rs61733482

chr5-37227766-A-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001384732.1(CPLANE1):c.1173T>G(p.Ala391=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000504 in 1,551,188 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: CPLANE1 NM_001384732.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.339

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 5-37227766-A-C is Benign according to our data. Variant chr5-37227766-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 511941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-37227766-A-C is described in Lovd as [Benign]. Variant chr5-37227766-A-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.339 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00268 (409/152328) while in subpopulation AFR AF= 0.00945 (393/41578). AF 95% confidence interval is 0.00868. There are 2 homozygotes in gnomad4. There are 206 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPLANE1	NM_001384732.1	c.1173T>G	p.Ala391=	synonymous_variant	10/53	ENST00000651892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPLANE1	ENST00000651892.2	c.1173T>G	p.Ala391=	synonymous_variant	10/53		NM_001384732.1	A2

Frequencies

GnomAD3 genomes AF: 0.00268 AC: 408 AN: 152210 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00946

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000606 AC: 95 AN: 156816 Hom.: 0 AF XY: 0.000373 AC XY: 31 AN XY: 83006

Gnomad AFR exome AF: 0.00941

Gnomad AMR exome AF: 0.000729

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000164

Gnomad OTH exome AF: 0.000227

GnomAD4 exome AF: 0.000267 AC: 373 AN: 1398860 Hom.: 0 Cov.: 31 AF XY: 0.000222 AC XY: 153 AN XY: 689970

Gnomad4 AFR exome AF: 0.00937

Gnomad4 AMR exome AF: 0.000700

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000111

Gnomad4 OTH exome AF: 0.000655

GnomAD4 genome AF: 0.00268 AC: 409 AN: 152328 Hom.: 2 Cov.: 33 AF XY: 0.00277 AC XY: 206 AN XY: 74484

Gnomad4 AFR AF: 0.00945

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00135 Hom.: 0

Bravo AF: 0.00321

Asia WGS AF: 0.000867 AC: 3 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 17, 2024	- -

not specified Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	7.2
Dann	Benign	0.64

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: rs61733482; hg19: chr5-37227868;