5-37169067-T-C

Variant names:

• chr5-37169067-T-C
• rs143147192
• NM_001384732.1:c.6957A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001384732.1(CPLANE1):​c.6957A>G​(p.Gln2319Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00717 in 1,614,242 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0066 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0072 (76 hom.)
• Consequence: CPLANE1 NM_001384732.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.155
• Publications: 5 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 5-37169067-T-C is Benign according to our data. Variant chr5-37169067-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 196922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.155 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0589 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.6957A>G	p.Gln2319Gln	synonymous	Exon 34 of 53	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.6957A>G	p.Gln2319Gln	synonymous	Exon 34 of 52	NP_075561.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	ENST00000651892.2	MANE Select	c.6957A>G	p.Gln2319Gln	synonymous	Exon 34 of 53	ENSP00000498265.2	A0A494BZW6
	CPLANE1	ENST00000514429.5	TSL:1	c.4101A>G	p.Gln1367Gln	synonymous	Exon 19 of 37	ENSP00000424223.1	H0Y9I8
	CPLANE1	ENST00000509849.5	TSL:1	n.3969A>G		non_coding_transcript_exon	Exon 19 of 37	ENSP00000426337.1	H0YA77

Frequencies

GnomAD3 genomes AF: 0.00662 AC: 1008 AN: 152242 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.00693

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00993

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00758

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.00750 AC: 1886 AN: 251412 AF XY: 0.00803

Gnomad AFR exome AF: 0.00135

Gnomad AMR exome AF: 0.00639

Gnomad ASJ exome AF: 0.0108

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0150

Gnomad NFE exome AF: 0.00767

Gnomad OTH exome AF: 0.0137

GnomAD4 exome AF: 0.00723 AC: 10565 AN: 1461882 Hom.: 76 Cov.: 32 AF XY: 0.00738 AC XY: 5365 AN XY: 727242

African (AFR) AF: 0.00385 AC: 129 AN: 33480

American (AMR) AF: 0.00622 AC: 278 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0102 AC: 267 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00872 AC: 752 AN: 86258

European-Finnish (FIN) AF: 0.0150 AC: 800 AN: 53420

Middle Eastern (MID) AF: 0.0643 AC: 371 AN: 5768

European-Non Finnish (NFE) AF: 0.00664 AC: 7380 AN: 1112002

Other (OTH) AF: 0.00974 AC: 588 AN: 60394

GnomAD4 genome AF: 0.00662 AC: 1009 AN: 152360 Hom.: 12 Cov.: 32 AF XY: 0.00711 AC XY: 530 AN XY: 74510

African (AFR) AF: 0.00175 AC: 73 AN: 41598

American (AMR) AF: 0.00692 AC: 106 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00835 AC: 29 AN: 3472

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

South Asian (SAS) AF: 0.00994 AC: 48 AN: 4828

European-Finnish (FIN) AF: 0.0146 AC: 155 AN: 10620

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00759 AC: 516 AN: 68028

Other (OTH) AF: 0.0161 AC: 34 AN: 2110

Alfa AF: 0.00667 Hom.: 8

Bravo AF: 0.00576

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.00949

EpiControl AF: 0.00966

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	2	Joubert syndrome 17 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.3
DANN	Benign	0.35
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs143147192; hg19: chr5-37169169; COSMIC: COSV57071951; COSMIC: COSV57071951;