rs10805625

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001384732.1(CPLANE1):​c.5901-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,598,720 control chromosomes in the GnomAD database, including 10,836 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1951 hom., cov: 32)
Exomes 𝑓: 0.11 ( 8885 hom. )

Consequence

CPLANE1
NM_001384732.1 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.00001170
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.723
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 5-37175989-A-G is Benign according to our data. Variant chr5-37175989-A-G is described in ClinVar as [Benign]. Clinvar id is 158046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-37175989-A-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CPLANE1NM_001384732.1 linkuse as main transcriptc.5901-3T>C splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000651892.2 NP_001371661.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CPLANE1ENST00000651892.2 linkuse as main transcriptc.5901-3T>C splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant NM_001384732.1 ENSP00000498265 A2

Frequencies

GnomAD3 genomes
AF:
0.147
AC:
22379
AN:
152030
Hom.:
1951
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.234
Gnomad AMI
AF:
0.0351
Gnomad AMR
AF:
0.161
Gnomad ASJ
AF:
0.149
Gnomad EAS
AF:
0.0546
Gnomad SAS
AF:
0.105
Gnomad FIN
AF:
0.134
Gnomad MID
AF:
0.111
Gnomad NFE
AF:
0.105
Gnomad OTH
AF:
0.156
GnomAD3 exomes
AF:
0.124
AC:
31046
AN:
250658
Hom.:
2139
AF XY:
0.119
AC XY:
16151
AN XY:
135474
show subpopulations
Gnomad AFR exome
AF:
0.233
Gnomad AMR exome
AF:
0.167
Gnomad ASJ exome
AF:
0.166
Gnomad EAS exome
AF:
0.0512
Gnomad SAS exome
AF:
0.103
Gnomad FIN exome
AF:
0.130
Gnomad NFE exome
AF:
0.108
Gnomad OTH exome
AF:
0.125
GnomAD4 exome
AF:
0.106
AC:
153643
AN:
1446572
Hom.:
8885
Cov.:
26
AF XY:
0.106
AC XY:
76231
AN XY:
720682
show subpopulations
Gnomad4 AFR exome
AF:
0.235
Gnomad4 AMR exome
AF:
0.164
Gnomad4 ASJ exome
AF:
0.164
Gnomad4 EAS exome
AF:
0.0359
Gnomad4 SAS exome
AF:
0.0996
Gnomad4 FIN exome
AF:
0.129
Gnomad4 NFE exome
AF:
0.0999
Gnomad4 OTH exome
AF:
0.117
GnomAD4 genome
AF:
0.147
AC:
22405
AN:
152148
Hom.:
1951
Cov.:
32
AF XY:
0.149
AC XY:
11069
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.234
Gnomad4 AMR
AF:
0.161
Gnomad4 ASJ
AF:
0.149
Gnomad4 EAS
AF:
0.0541
Gnomad4 SAS
AF:
0.105
Gnomad4 FIN
AF:
0.134
Gnomad4 NFE
AF:
0.104
Gnomad4 OTH
AF:
0.158
Alfa
AF:
0.127
Hom.:
618
Bravo
AF:
0.151
Asia WGS
AF:
0.139
AC:
481
AN:
3476
EpiCase
AF:
0.117
EpiControl
AF:
0.115

ClinVar

Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Benign, criteria provided, single submitterclinical testingGeneDxMar 14, 2016This 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 submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Likely benign, no assertion criteria providedclinical testingGenetic Services Laboratory, University of Chicago-- -
Joubert syndrome 17 Benign:3
Benign, criteria provided, single submitterclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical CenterSep 21, 2015- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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. -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.63
DANN
Benign
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000012
dbscSNV1_RF
Benign
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10805625; hg19: chr5-37176091; COSMIC: COSV57071349; API