chr5-37106960-C-T

Variant names:

• chr5-37106960-C-T
• rs543018376
• NM_001384732.1:c.*642G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_001384732.1(CPLANE1):​c.*642G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 985,388 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (3 hom.)
• Consequence: CPLANE1 NM_001384732.1 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0900
• Publications: 1 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00117 (178/152290) while in subpopulation SAS AF = 0.00414 (20/4826). AF 95% confidence interval is 0.00275. There are 0 homozygotes in GnomAd4. There are 106 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAdExome4 at 3 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	NM_001384732.1	MANE Select	c.*642G>A		3_prime_UTR	Exon 53 of 53	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.*642G>A		3_prime_UTR	Exon 52 of 52	NP_075561.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	ENST00000651892.2	MANE Select	c.*642G>A		3_prime_UTR	Exon 53 of 53	ENSP00000498265.2	A0A494BZW6
	CPLANE1	ENST00000508244.5	TSL:5	c.*642G>A		3_prime_UTR	Exon 51 of 51	ENSP00000421690.1	Q9H799-1
	CPLANE1	ENST00000913843.1		c.*642G>A		3_prime_UTR	Exon 52 of 52	ENSP00000583902.1

Frequencies

GnomAD3 genomes AF: 0.00117 AC: 178 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00128

Gnomad OTH AF: 0.000957

GnomAD4 exome AF: 0.00207 AC: 1723 AN: 833098 Hom.: 3 Cov.: 30 AF XY: 0.00223 AC XY: 859 AN XY: 384712

African (AFR) AF: 0.000127 AC: 2 AN: 15786

American (AMR) AF: 0.00102 AC: 1 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.00136 AC: 7 AN: 5152

East Asian (EAS) AF: 0.00 AC: 0 AN: 3630

South Asian (SAS) AF: 0.00553 AC: 91 AN: 16460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 278

Middle Eastern (MID) AF: 0.00247 AC: 4 AN: 1620

European-Non Finnish (NFE) AF: 0.00205 AC: 1562 AN: 761892

Other (OTH) AF: 0.00205 AC: 56 AN: 27296

GnomAD4 genome AF: 0.00117 AC: 178 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.00142 AC XY: 106 AN XY: 74462

African (AFR) AF: 0.000265 AC: 11 AN: 41556

American (AMR) AF: 0.00340 AC: 52 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4826

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00128 AC: 87 AN: 68024

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00125 Hom.: 0

Bravo AF: 0.00117

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Joubert syndrome 17 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.32
PhyloP100		-0.090
Mutation Taster		=100/0	polymorphism

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: rs543018376; hg19: chr5-37107062;