rs16903511

Variant names:

• chr5-37121664-G-C
• rs16903511
• NM_001384732.1:c.9138C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001384732.1(CPLANE1):​c.9138C>G​(p.Pro3046Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,614,124 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (66 hom.)
• Consequence: CPLANE1 NM_001384732.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.119
• Publications: 4 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, ClinGen, G2P, Illumina, Labcorp Genetics (formerly Invitae)
• orofaciodigital syndrome type 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• 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=-0.84).
• BP6: Variant 5-37121664-G-C is Benign according to our data. Variant chr5-37121664-G-C is described in ClinVar as Benign. ClinVar VariationId is 158059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00383 (584/152296) while in subpopulation AMR AF = 0.028 (428/15292). AF 95% confidence interval is 0.0258. There are 12 homozygotes in GnomAd4. There are 304 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	NM_001384732.1	MANE Select	c.9138C>G	p.Pro3046Pro	synonymous	Exon 49 of 53	NP_001371661.1
	CPLANE1	NM_023073.4		c.8976C>G	p.Pro2992Pro	synonymous	Exon 48 of 52	NP_075561.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	ENST00000651892.2	MANE Select	c.9138C>G	p.Pro3046Pro	synonymous	Exon 49 of 53	ENSP00000498265.2
	CPLANE1	ENST00000514429.5	TSL:1	c.6174C>G	p.Pro2058Pro	synonymous	Exon 33 of 37	ENSP00000424223.1
	CPLANE1	ENST00000509849.5	TSL:1	n.*480C>G		non_coding_transcript_exon	Exon 33 of 37	ENSP00000426337.1

Frequencies

GnomAD3 genomes AF: 0.00385 AC: 586 AN: 152178 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0222

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00819 AC: 2060 AN: 251432 AF XY: 0.00661

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.0477

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0190

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00472

GnomAD4 exome AF: 0.00208 AC: 3041 AN: 1461828 Hom.: 66 Cov.: 31 AF XY: 0.00190 AC XY: 1379 AN XY: 727218

African (AFR) AF: 0.000418 AC: 14 AN: 33478

American (AMR) AF: 0.0456 AC: 2037 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0199 AC: 790 AN: 39694

South Asian (SAS) AF: 0.000800 AC: 69 AN: 86252

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111976

Other (OTH) AF: 0.00195 AC: 118 AN: 60392

GnomAD4 genome AF: 0.00383 AC: 584 AN: 152296 Hom.: 12 Cov.: 32 AF XY: 0.00408 AC XY: 304 AN XY: 74482

African (AFR) AF: 0.000481 AC: 20 AN: 41572

American (AMR) AF: 0.0280 AC: 428 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0222 AC: 115 AN: 5176

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68016

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.000974 Hom.: 0

Bravo AF: 0.00651

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	Joubert syndrome 17 (1)
-	-	1	Orofaciodigital syndrome type 6;C3553264:Joubert syndrome 17 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.79
DANN	Benign	0.36
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16903511; hg19: chr5-37121766; COSMIC: COSV57061534; COSMIC: COSV57061534;