NM_001384732.1:c.5900+7G>T

Variant names:

• chr5-37177614-C-A
• rs78315844
• NM_001384732.1:c.5900+7G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001384732.1(CPLANE1):​c.5900+7G>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 0.00598 in 1,608,220 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (61 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (76 hom.)
• Consequence: CPLANE1 NM_001384732.1 splice_region, intron
• Scores: Splicing: ADA: 0.00001557
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.536
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-37177614-C-A is Benign according to our data. Variant chr5-37177614-C-A is described in ClinVar as Benign. ClinVar VariationId is 158045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0508 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.5900+7G>T		splice_region intron	N/A	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.5900+7G>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.5900+7G>T		splice_region intron	N/A	ENSP00000498265.2	A0A494BZW6
	CPLANE1	ENST00000514429.5	TSL:1	c.3044+7G>T		splice_region intron	N/A	ENSP00000424223.1	H0Y9I8
	CPLANE1	ENST00000509849.5	TSL:1	n.2912+7G>T		splice_region intron	N/A	ENSP00000426337.1	H0YA77

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2631 AN: 152048 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0527

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.00337

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00735 AC: 1838 AN: 250132 AF XY: 0.00705

Gnomad AFR exome AF: 0.0546

Gnomad AMR exome AF: 0.00540

Gnomad ASJ exome AF: 0.000499

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.00401

Gnomad OTH exome AF: 0.00574

GnomAD4 exome AF: 0.00479 AC: 6978 AN: 1456054 Hom.: 76 Cov.: 28 AF XY: 0.00498 AC XY: 3611 AN XY: 724702

African (AFR) AF: 0.0559 AC: 1859 AN: 33242

American (AMR) AF: 0.00573 AC: 254 AN: 44344

Ashkenazi Jewish (ASJ) AF: 0.000422 AC: 11 AN: 26048

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39618

South Asian (SAS) AF: 0.0101 AC: 865 AN: 85834

European-Finnish (FIN) AF: 0.000131 AC: 7 AN: 53392

Middle Eastern (MID) AF: 0.0225 AC: 129 AN: 5738

European-Non Finnish (NFE) AF: 0.00309 AC: 3418 AN: 1107654

Other (OTH) AF: 0.00721 AC: 434 AN: 60184

GnomAD4 genome AF: 0.0173 AC: 2635 AN: 152166 Hom.: 61 Cov.: 32 AF XY: 0.0169 AC XY: 1261 AN XY: 74404

African (AFR) AF: 0.0526 AC: 2185 AN: 41514

American (AMR) AF: 0.00804 AC: 123 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000866 AC: 3 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00996 AC: 48 AN: 4820

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10574

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.00337 AC: 229 AN: 68000

Other (OTH) AF: 0.0166 AC: 35 AN: 2112

Alfa AF: 0.00780 Hom.: 10

Bravo AF: 0.0198

EpiCase AF: 0.00382

EpiControl AF: 0.00658

ClinVar

ClinVar submissions

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	-0.90
CADD	Benign	1.2
DANN	Benign	0.28
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0060
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: rs78315844; hg19: chr5-37177716;