Variant 5-37195874-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001384732.1(CPLANE1):c.3795T>A(p.Val1265=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00564 in 1,610,988 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 49 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 67 hom. )

Consequence

CPLANE1
NM_001384732.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.01

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 5-37195874-A-T is Benign according to our data. Variant chr5-37195874-A-T is described in ClinVar as [Benign]. Clinvar id is 158033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-37195874-A-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0155 (2366/152236) while in subpopulation AFR AF= 0.0469 (1948/41530). AF 95% confidence interval is 0.0452. There are 49 homozygotes in gnomad4. There are 1135 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 49 Mitochondrial gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPLANE1	NM_001384732.1 linkuse as main transcript	c.3795T>A	p.Val1265=	synonymous_variant	21/53	ENST00000651892.2	NP_001371661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPLANE1	ENST00000651892.2 linkuse as main transcript	c.3795T>A	p.Val1265=	synonymous_variant	21/53		NM_001384732.1	ENSP00000498265	A2

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2362

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0469

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00694

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00331

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00685

AC:

1700

AN:

248134

Hom.:

AF XY:

0.00663

AC XY:

890

AN XY:

134182

show subpopulations

Gnomad AFR exome

AF:

0.0485

Gnomad AMR exome

AF:

0.00504

Gnomad ASJ exome

AF:

0.000501

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00887

Gnomad FIN exome

AF:

0.0000926

Gnomad NFE exome

AF:

0.00393

Gnomad OTH exome

AF:

0.00548

GnomAD4 exome

AF:

0.00461

AC:

6720

AN:

1458752

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

3495

AN XY:

725652

show subpopulations

Gnomad4 AFR exome

AF:

0.0502

Gnomad4 AMR exome

AF:

0.00542

Gnomad4 ASJ exome

AF:

0.000423

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00306

Gnomad4 OTH exome

AF:

0.00664

GnomAD4 genome

AF:

0.0155

AC:

2366

AN:

152236

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

1135

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0469

Gnomad4 AMR

AF:

0.00693

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00995

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00331

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00646

Hom.:

Bravo

AF:

0.0177

Asia WGS

AF:

0.00289

AC:

AN:

3476

EpiCase

AF:

0.00369

EpiControl

AF:

0.00645

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 23, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Joubert syndrome 17

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.2

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.25

Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over