rs6884652

Variant names:

• chr5-37170076-T-C
• rs6884652
• NM_001384732.1:c.6427A>G

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.6427A>G​(p.Ile2143Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00859 in 1,614,086 control chromosomes in the GnomAD database, including 1,004 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (548 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (456 hom.)
• Consequence: CPLANE1 NM_001384732.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.419
• Publications: 8 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 (MetaRNN=0.0015473962).
• BP6: Variant 5-37170076-T-C is Benign according to our data. Variant chr5-37170076-T-C is described in ClinVar as Benign. ClinVar VariationId is 158049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 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.6427A>G	p.Ile2143Val	missense	Exon 33 of 53	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.6427A>G	p.Ile2143Val	missense	Exon 33 of 52	NP_075561.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	ENST00000651892.2	MANE Select	c.6427A>G	p.Ile2143Val	missense	Exon 33 of 53	ENSP00000498265.2	A0A494BZW6
	CPLANE1	ENST00000514429.5	TSL:1	c.3571A>G	p.Ile1191Val	missense	Exon 18 of 37	ENSP00000424223.1	H0Y9I8
	CPLANE1	ENST00000509849.5	TSL:1	n.3439A>G		non_coding_transcript_exon	Exon 18 of 37	ENSP00000426337.1	H0YA77

Frequencies

GnomAD3 genomes AF: 0.0457 AC: 6949 AN: 152096 Hom.: 549 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0292

GnomAD2 exomes AF: 0.0118 AC: 2954 AN: 251208 AF XY: 0.00852

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.00778

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000528

Gnomad OTH exome AF: 0.00555

GnomAD4 exome AF: 0.00473 AC: 6916 AN: 1461872 Hom.: 456 Cov.: 31 AF XY: 0.00397 AC XY: 2887 AN XY: 727242

African (AFR) AF: 0.162 AC: 5416 AN: 33466

American (AMR) AF: 0.00914 AC: 409 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000383 AC: 33 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00815 AC: 47 AN: 5768

European-Non Finnish (NFE) AF: 0.000318 AC: 354 AN: 1112010

Other (OTH) AF: 0.0108 AC: 655 AN: 60394

GnomAD4 genome AF: 0.0457 AC: 6949 AN: 152214 Hom.: 548 Cov.: 32 AF XY: 0.0437 AC XY: 3256 AN XY: 74442

African (AFR) AF: 0.159 AC: 6600 AN: 41496

American (AMR) AF: 0.0159 AC: 243 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68014

Other (OTH) AF: 0.0289 AC: 61 AN: 2108

Alfa AF: 0.0191 Hom.: 379

Bravo AF: 0.0519

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.152 AC: 668

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0145 AC: 1758

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000711

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	not provided (3)
-	-	1	Joubert syndrome 17 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.46
DANN	Benign	0.13
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.42
PROVEAN	Benign	0.11	N
REVEL	Benign	0.022
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.0060
MPC		0.10
ClinPred		0.00061	T
GERP RS		1.4
Varity_R		0.028
gMVP		0.11
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6884652; hg19: chr5-37170178;