NM_001384732.1:c.*807A>G

Variant names:

• chr5-37106795-T-C
• rs78011227
• NM_001384732.1:c.*807A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001384732.1(CPLANE1):​c.*807A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000881 in 946,754 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: CPLANE1 NM_001384732.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.301
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-37106795-T-C is Benign according to our data. Variant chr5-37106795-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 353403.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00387 (589/152360) while in subpopulation AFR AF = 0.0135 (560/41592). AF 95% confidence interval is 0.0125. There are 5 homozygotes in GnomAd4. There are 270 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 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.*807A>G		3_prime_UTR	Exon 53 of 53	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.*807A>G		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.*807A>G		3_prime_UTR	Exon 53 of 53	ENSP00000498265.2	A0A494BZW6
	CPLANE1	ENST00000508244.5	TSL:5	c.*807A>G		3_prime_UTR	Exon 51 of 51	ENSP00000421690.1	Q9H799-1
	CPLANE1	ENST00000913843.1		c.*807A>G		3_prime_UTR	Exon 52 of 52	ENSP00000583902.1

Frequencies

GnomAD3 genomes AF: 0.00388 AC: 591 AN: 152242 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000955

GnomAD4 exome AF: 0.000308 AC: 245 AN: 794394 Hom.: 0 Cov.: 12 AF XY: 0.000280 AC XY: 103 AN XY: 368170

African (AFR) AF: 0.0130 AC: 194 AN: 14958

American (AMR) AF: 0.00 AC: 0 AN: 924

Ashkenazi Jewish (ASJ) AF: 0.000204 AC: 1 AN: 4908

East Asian (EAS) AF: 0.00 AC: 0 AN: 3418

South Asian (SAS) AF: 0.00 AC: 0 AN: 15604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 256

Middle Eastern (MID) AF: 0.000644 AC: 1 AN: 1554

European-Non Finnish (NFE) AF: 0.0000482 AC: 35 AN: 726800

Other (OTH) AF: 0.000539 AC: 14 AN: 25972

GnomAD4 genome AF: 0.00387 AC: 589 AN: 152360 Hom.: 5 Cov.: 32 AF XY: 0.00362 AC XY: 270 AN XY: 74510

African (AFR) AF: 0.0135 AC: 560 AN: 41592

American (AMR) AF: 0.00124 AC: 19 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68026

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00275 Hom.: 1

Bravo AF: 0.00450

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

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	1.6
DANN	Benign	0.70
PhyloP100		0.30
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: rs78011227; hg19: chr5-37106897;