rs1473295

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_201548.5(CERKL):c.156C>T(p.Phe52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,601,126 control chromosomes in the GnomAD database, including 202,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15414 hom., cov: 32)

Exomes 𝑓: 0.50 ( 186674 hom. )

Consequence

CERKL
NM_201548.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.539

Variant links:

Genes affected

CERKL (HGNC:21699): (ceramide kinase like) This gene was initially identified as a locus (RP26) associated with an autosomal recessive form of retinitis pigmentosa (arRP) disease. This gene encodes a protein with ceramide kinase-like domains, however, the protein does not phosphorylate ceramide and its target substrate is currently unknown. This protein may be a negative regulator of apoptosis in photoreceptor cells. Mutations in this gene cause a form of retinitis pigmentosa characterized by autosomal recessive cone and rod dystrophy (arCRD). Alternative splicing of this gene results in multiple transcript variants encoding different isoforms and non-coding transcripts.[provided by RefSeq, May 2010]

CERKL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 2-181656851-G-A is Benign according to our data. Variant chr2-181656851-G-A is described in ClinVar as [Benign]. Clinvar id is 166849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-181656851-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.539 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERKL	NM_201548.5 linkuse as main transcript	c.156C>T	p.Phe52=	synonymous_variant	1/13	ENST00000410087.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERKL	ENST00000410087.8 linkuse as main transcript	c.156C>T	p.Phe52=	synonymous_variant	1/13	1	NM_201548.5	P1	Q49MI3-2

Frequencies

GnomAD3 genomes

AF:

0.426

AC:

64701

AN:

151874

Hom.:

15429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.530

Gnomad ASJ

AF:

0.548

Gnomad EAS

AF:

0.727

Gnomad SAS

AF:

0.774

Gnomad FIN

AF:

0.406

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.474

Gnomad OTH

AF:

0.463

GnomAD3 exomes

AF:

0.528

AC:

126651

AN:

240042

Hom.:

36084

AF XY:

0.540

AC XY:

70537

AN XY:

130662

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.608

Gnomad ASJ exome

AF:

0.534

Gnomad EAS exome

AF:

0.711

Gnomad SAS exome

AF:

0.784

Gnomad FIN exome

AF:

0.394

Gnomad NFE exome

AF:

0.468

Gnomad OTH exome

AF:

0.510

GnomAD4 exome

AF:

0.498

AC:

721361

AN:

1449134

Hom.:

186674

Cov.:

AF XY:

0.507

AC XY:

364263

AN XY:

718744

show subpopulations

Gnomad4 AFR exome

AF:

0.221

Gnomad4 AMR exome

AF:

0.600

Gnomad4 ASJ exome

AF:

0.540

Gnomad4 EAS exome

AF:

0.729

Gnomad4 SAS exome

AF:

0.783

Gnomad4 FIN exome

AF:

0.395

Gnomad4 NFE exome

AF:

0.475

Gnomad4 OTH exome

AF:

0.503

GnomAD4 genome

AF:

0.426

AC:

64696

AN:

151992

Hom.:

15414

Cov.:

AF XY:

0.434

AC XY:

32212

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.227

Gnomad4 AMR

AF:

0.530

Gnomad4 ASJ

AF:

0.548

Gnomad4 EAS

AF:

0.727

Gnomad4 SAS

AF:

0.774

Gnomad4 FIN

AF:

0.406

Gnomad4 NFE

AF:

0.474

Gnomad4 OTH

AF:

0.460

Alfa

AF:

0.470

Hom.:

30803

Bravo

AF:

0.422

Asia WGS

AF:

0.671

AC:

2333

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 29, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 03, 2021	- -

Retinitis pigmentosa 26

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 19, 2019	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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

-0.37

Cadd

Benign

Dann

Benign

0.94

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

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