rs13356183

Variant names:

• chr5-37226858-C-T
• rs13356183
• NM_001384732.1:c.1737G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001384732.1(CPLANE1):​c.1737G>A​(p.Ala579Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,551,234 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (44 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (64 hom.)
• Consequence: CPLANE1 NM_001384732.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.693
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 5-37226858-C-T is Benign according to our data. Variant chr5-37226858-C-T is described in ClinVar as Benign. ClinVar VariationId is 158027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.693 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.051 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.1737G>A	p.Ala579Ala	synonymous	Exon 12 of 53	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.1737G>A	p.Ala579Ala	synonymous	Exon 12 of 52	NP_075561.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	ENST00000651892.2	MANE Select	c.1737G>A	p.Ala579Ala	synonymous	Exon 12 of 53	ENSP00000498265.2	A0A494BZW6
	CPLANE1	ENST00000955438.1		c.1737G>A	p.Ala579Ala	synonymous	Exon 12 of 53	ENSP00000625497.1
	CPLANE1	ENST00000508244.5	TSL:5	c.1737G>A	p.Ala579Ala	synonymous	Exon 11 of 51	ENSP00000421690.1	Q9H799-1

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 2005 AN: 152110 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.0453

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.00910

GnomAD2 exomes AF: 0.00315 AC: 493 AN: 156314 AF XY: 0.00242

Gnomad AFR exome AF: 0.0487

Gnomad AMR exome AF: 0.00281

Gnomad ASJ exome AF: 0.000118

Gnomad EAS exome AF: 0.0000918

Gnomad FIN exome AF: 0.0000592

Gnomad NFE exome AF: 0.000298

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00161 AC: 2247 AN: 1399006 Hom.: 64 Cov.: 32 AF XY: 0.00143 AC XY: 988 AN XY: 689928

African (AFR) AF: 0.0531 AC: 1677 AN: 31580

American (AMR) AF: 0.00280 AC: 100 AN: 35670

Ashkenazi Jewish (ASJ) AF: 0.000278 AC: 7 AN: 25168

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35686

South Asian (SAS) AF: 0.000316 AC: 25 AN: 79146

European-Finnish (FIN) AF: 0.0000407 AC: 2 AN: 49182

Middle Eastern (MID) AF: 0.00369 AC: 21 AN: 5694

European-Non Finnish (NFE) AF: 0.000187 AC: 202 AN: 1078848

Other (OTH) AF: 0.00365 AC: 212 AN: 58032

GnomAD4 genome AF: 0.0133 AC: 2022 AN: 152228 Hom.: 44 Cov.: 32 AF XY: 0.0135 AC XY: 1002 AN XY: 74418

African (AFR) AF: 0.0455 AC: 1892 AN: 41538

American (AMR) AF: 0.00516 AC: 79 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68000

Other (OTH) AF: 0.00900 AC: 19 AN: 2110

Alfa AF: 0.00559 Hom.: 7

Bravo AF: 0.0153

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Joubert syndrome 17 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.5
DANN	Benign	0.43
PhyloP100		-0.69
Mutation Taster		=294/6	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: rs13356183; hg19: chr5-37226960;