rs587783353

Variant names:

• chr5-37138851-T-A
• rs58401892
• NM_001384732.1:c.8664-3A>T

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.8664-3A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,596,260 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (42 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (35 hom.)
• Consequence: CPLANE1 NM_001384732.1 splice_region, intron
• Scores: Splicing: ADA: 0.0002522
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.58
• 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: Labcorp Genetics (formerly Invitae), Illumina, G2P, ClinGen, Laboratory for Molecular Medicine
• 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=-0.48).
• BP6: Variant 5-37138851-T-A is Benign according to our data. Variant chr5-37138851-T-A is described in ClinVar as Benign. ClinVar VariationId is 158056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0128 (1948/152336) while in subpopulation AFR AF = 0.0446 (1855/41568). AF 95% confidence interval is 0.0429. There are 42 homozygotes in GnomAd4. There are 910 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 42 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.8664-3A>T		splice_region intron	N/A	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.8502-3A>T		splice_region intron	N/A	NP_075561.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	ENST00000651892.2	MANE Select	c.8664-3A>T		splice_region intron	N/A	ENSP00000498265.2	A0A494BZW6
	CPLANE1	ENST00000514429.5	TSL:1	c.5700-3A>T		splice_region intron	N/A	ENSP00000424223.1	H0Y9I8
	CPLANE1	ENST00000509849.5	TSL:1	n.5645-3A>T		splice_region intron	N/A	ENSP00000426337.1	H0YA77

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1948 AN: 152218 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.0448

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00348 AC: 810 AN: 232856 AF XY: 0.00252

Gnomad AFR exome AF: 0.0457

Gnomad AMR exome AF: 0.00213

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000147

Gnomad OTH exome AF: 0.00106

GnomAD4 exome AF: 0.00132 AC: 1906 AN: 1443924 Hom.: 35 Cov.: 30 AF XY: 0.00114 AC XY: 816 AN XY: 717846

African (AFR) AF: 0.0469 AC: 1525 AN: 32482

American (AMR) AF: 0.00229 AC: 89 AN: 38932

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25198

East Asian (EAS) AF: 0.00 AC: 0 AN: 39420

South Asian (SAS) AF: 0.000122 AC: 10 AN: 81914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53216

Middle Eastern (MID) AF: 0.00158 AC: 9 AN: 5680

European-Non Finnish (NFE) AF: 0.0000921 AC: 102 AN: 1107422

Other (OTH) AF: 0.00287 AC: 171 AN: 59660

GnomAD4 genome AF: 0.0128 AC: 1948 AN: 152336 Hom.: 42 Cov.: 32 AF XY: 0.0122 AC XY: 910 AN XY: 74492

African (AFR) AF: 0.0446 AC: 1855 AN: 41568

American (AMR) AF: 0.00398 AC: 61 AN: 15310

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68034

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.00395 Hom.: 1

Bravo AF: 0.0147

Asia WGS AF: 0.00115 AC: 4 AN: 3476

ClinVar

ClinVar submissions as Germline

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	-0.48
CADD	Benign	10
DANN	Benign	0.80
PhyloP100		1.6
Mutation Taster		=10/90	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00025
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: rs58401892; hg19: chr5-37138953;