rs10805625

Variant names:

• chr5-37175989-A-G
• rs10805625
• NM_001384732.1:c.5901-3T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001384732.1(CPLANE1):​c.5901-3T>C variant causes a splice region, 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, intron
• Scores: Splicing: ADA: 0.00001170
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.723
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• Joubert syndrome 17

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Illumina
• orofaciodigital syndrome type 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 158046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384732.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	NM_001384732.1	MANE Select	c.5901-3T>C		splice_region intron	N/A	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.5901-3T>C		splice_region intron	N/A	NP_075561.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	ENST00000651892.2	MANE Select	c.5901-3T>C		splice_region intron	N/A	ENSP00000498265.2	A0A494BZW6
	CPLANE1	ENST00000514429.5	TSL:1	c.3045-3T>C		splice_region intron	N/A	ENSP00000424223.1	H0Y9I8
	CPLANE1	ENST00000511781.1	TSL:1	n.111T>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22379 AN: 152030 Hom.: 1951 Cov.: 32

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

GnomAD2 exomes AF: 0.124 AC: 31046 AN: 250658 AF XY: 0.119

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 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

African (AFR) AF: 0.235 AC: 7756 AN: 33042

American (AMR) AF: 0.164 AC: 7300 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 4255 AN: 26024

East Asian (EAS) AF: 0.0359 AC: 1421 AN: 39568

South Asian (SAS) AF: 0.0996 AC: 8541 AN: 85766

European-Finnish (FIN) AF: 0.129 AC: 6852 AN: 53298

Middle Eastern (MID) AF: 0.133 AC: 755 AN: 5660

European-Non Finnish (NFE) AF: 0.0999 AC: 109773 AN: 1098778

Other (OTH) AF: 0.117 AC: 6990 AN: 59844

GnomAD4 genome AF: 0.147 AC: 22405 AN: 152148 Hom.: 1951 Cov.: 32 AF XY: 0.149 AC XY: 11069 AN XY: 74394

African (AFR) AF: 0.234 AC: 9715 AN: 41474

American (AMR) AF: 0.161 AC: 2460 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3468

East Asian (EAS) AF: 0.0541 AC: 281 AN: 5190

South Asian (SAS) AF: 0.105 AC: 506 AN: 4824

European-Finnish (FIN) AF: 0.134 AC: 1424 AN: 10590

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7105 AN: 68002

Other (OTH) AF: 0.158 AC: 333 AN: 2112

Alfa AF: 0.130 Hom.: 692

Bravo AF: 0.151

Asia WGS AF: 0.139 AC: 481 AN: 3476

EpiCase AF: 0.117

EpiControl AF: 0.115

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Joubert syndrome 17 (3)
-	-	3	not specified (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.63
DANN	Benign	0.34
PhyloP100		-0.72
Mutation Taster		=85/15	polymorphism (auto)

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

Other links and lift over

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