NM_001384732.1:c.*833T>C

Variant names:

• chr5-37106769-A-G
• rs553022771
• NM_001384732.1:c.*833T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_001384732.1(CPLANE1):​c.*833T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000571 in 858,436 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: CPLANE1 NM_001384732.1 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0630
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000289 (44/152374) while in subpopulation AMR AF = 0.00281 (43/15302). AF 95% confidence interval is 0.00214. There are 1 homozygotes in GnomAd4. There are 24 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

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.*833T>C		3_prime_UTR	Exon 53 of 53	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.*833T>C		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.*833T>C		3_prime_UTR	Exon 53 of 53	ENSP00000498265.2	A0A494BZW6
	CPLANE1	ENST00000508244.5	TSL:5	c.*833T>C		3_prime_UTR	Exon 51 of 51	ENSP00000421690.1	Q9H799-1
	CPLANE1	ENST00000913843.1		c.*833T>C		3_prime_UTR	Exon 52 of 52	ENSP00000583902.1

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 152256 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000708 AC: 5 AN: 706062 Hom.: 0 Cov.: 9 AF XY: 0.00000609 AC XY: 2 AN XY: 328622

African (AFR) AF: 0.00 AC: 0 AN: 13162

American (AMR) AF: 0.00123 AC: 1 AN: 816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4360

East Asian (EAS) AF: 0.00 AC: 0 AN: 2996

South Asian (SAS) AF: 0.00 AC: 0 AN: 13830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1362

European-Non Finnish (NFE) AF: 0.00000619 AC: 4 AN: 646268

Other (OTH) AF: 0.00 AC: 0 AN: 23028

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152374 Hom.: 1 Cov.: 32 AF XY: 0.000322 AC XY: 24 AN XY: 74512

African (AFR) AF: 0.0000240 AC: 1 AN: 41588

American (AMR) AF: 0.00281 AC: 43 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

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: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000249

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	-0.93
CADD	Benign	0.70
DANN	Benign	0.29
PhyloP100		-0.063

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: rs553022771; hg19: chr5-37106871;