NM_001384732.1:c.4190-10_4190-9delTT

Variant names:

• chr5-37185087-GAA-G
• rs111508546
• NM_001384732.1:c.4190-10_4190-9delTT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001384732.1(CPLANE1):​c.4190-10_4190-9delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00659 in 1,588,058 control chromosomes in the GnomAD database, including 611 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (335 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (276 hom.)
• Consequence: CPLANE1 NM_001384732.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.774
• Publications: 3 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, ClinGen, G2P, Illumina, Labcorp Genetics (formerly Invitae)
• 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 -16 ACMG points.

• BP6: Variant 5-37185087-GAA-G is Benign according to our data. Variant chr5-37185087-GAA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 195905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 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.4190-10_4190-9delTT		intron	N/A	NP_001371661.1
	CPLANE1	NM_023073.4		c.4190-10_4190-9delTT		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.4190-10_4190-9delTT		intron	N/A	ENSP00000498265.2
	CPLANE1	ENST00000514429.5	TSL:1	c.1334-10_1334-9delTT		intron	N/A	ENSP00000424223.1
	CPLANE1	ENST00000509849.5	TSL:1	n.1205-10_1205-9delTT		intron	N/A	ENSP00000426337.1

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5469 AN: 152092 Hom.: 335 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0287

GnomAD2 exomes AF: 0.00938 AC: 2094 AN: 223192 AF XY: 0.00678

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.00588

Gnomad ASJ exome AF: 0.000382

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.00386

GnomAD4 exome AF: 0.00347 AC: 4984 AN: 1435848 Hom.: 276 AF XY: 0.00297 AC XY: 2121 AN XY: 713484

African (AFR) AF: 0.128 AC: 4054 AN: 31770

American (AMR) AF: 0.00638 AC: 243 AN: 38082

Ashkenazi Jewish (ASJ) AF: 0.000204 AC: 5 AN: 24470

East Asian (EAS) AF: 0.00 AC: 0 AN: 39518

South Asian (SAS) AF: 0.000196 AC: 16 AN: 81662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52486

Middle Eastern (MID) AF: 0.00627 AC: 35 AN: 5578

European-Non Finnish (NFE) AF: 0.000165 AC: 182 AN: 1103180

Other (OTH) AF: 0.00760 AC: 449 AN: 59102

GnomAD4 genome AF: 0.0360 AC: 5476 AN: 152210 Hom.: 335 Cov.: 32 AF XY: 0.0344 AC XY: 2561 AN XY: 74424

African (AFR) AF: 0.125 AC: 5173 AN: 41514

American (AMR) AF: 0.0140 AC: 214 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68006

Other (OTH) AF: 0.0284 AC: 60 AN: 2116

Alfa AF: 0.0180 Hom.: 15

Bravo AF: 0.0401

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Joubert syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs111508546; hg19: chr5-37185189;