rs75549748

Variant names:

• chr5-37106713-T-C
• rs75549748
• NM_001384732.1:c.*889A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001384732.1(CPLANE1):​c.*889A>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 0.00663 in 440,250 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (75 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (14 hom.)
• Consequence: CPLANE1 NM_001384732.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.65
• 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: 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-37106713-T-C is Benign according to our data. Variant chr5-37106713-T-C is described in ClinVar as Benign. ClinVar VariationId is 353401.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0572 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.*889A>G		3_prime_UTR	Exon 53 of 53	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.*889A>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.*889A>G		3_prime_UTR	Exon 53 of 53	ENSP00000498265.2	A0A494BZW6
	CPLANE1	ENST00000508244.5	TSL:5	c.*889A>G		3_prime_UTR	Exon 51 of 51	ENSP00000421690.1	Q9H799-1
	CPLANE1	ENST00000913843.1		c.*889A>G		3_prime_UTR	Exon 52 of 52	ENSP00000583902.1

Frequencies

GnomAD3 genomes AF: 0.0167 AC: 2540 AN: 152180 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.0590

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00438

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: 0.000132

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00127 AC: 366 AN: 287952 Hom.: 14 Cov.: 5 AF XY: 0.00129 AC XY: 176 AN XY: 136960

African (AFR) AF: 0.0607 AC: 326 AN: 5370

American (AMR) AF: 0.00 AC: 0 AN: 302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1760

East Asian (EAS) AF: 0.00 AC: 0 AN: 1154

South Asian (SAS) AF: 0.00 AC: 0 AN: 5472

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 74

Middle Eastern (MID) AF: 0.00356 AC: 2 AN: 562

European-Non Finnish (NFE) AF: 0.0000114 AC: 3 AN: 264044

Other (OTH) AF: 0.00380 AC: 35 AN: 9214

GnomAD4 genome AF: 0.0168 AC: 2554 AN: 152298 Hom.: 75 Cov.: 32 AF XY: 0.0161 AC XY: 1201 AN XY: 74472

African (AFR) AF: 0.0591 AC: 2456 AN: 41546

American (AMR) AF: 0.00438 AC: 67 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68030

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.0126 Hom.: 5

Bravo AF: 0.0186

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.91
CADD	Benign	3.4
DANN	Benign	0.56
PhyloP100		1.6
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: rs75549748; hg19: chr5-37106815;