rs1473295

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_201548.5(CERKL):c.156C>T(p.Phe52Phe) 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:12

Conservation

PhyloP100: 0.539

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

CERKL-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
retinitis pigmentosa 26
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CERKL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 166849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
CERKL	NM_201548.5 link	c.156C>T	p.Phe52Phe	synonymous_variant	Exon 1 of 13	ENST00000410087.8	NP_963842.1	Q49MI3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERKL	ENST00000410087.8 link	c.156C>T	p.Phe52Phe	synonymous_variant	Exon 1 of 13	1	NM_201548.5	ENSP00000386725.3		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

GnomAD2 exomes

AF:

0.528

AC:

126651

AN:

240042

AF XY:

0.540

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 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

African (AFR)

AF:

0.221

AC:

7248

AN:

32824

American (AMR)

AF:

0.600

AC:

26596

AN:

44322

Ashkenazi Jewish (ASJ)

AF:

0.540

AC:

13983

AN:

25892

East Asian (EAS)

AF:

0.729

AC:

28415

AN:

39004

South Asian (SAS)

AF:

0.783

AC:

66953

AN:

85504

European-Finnish (FIN)

AF:

0.395

AC:

20832

AN:

52806

Middle Eastern (MID)

AF:

0.565

AC:

3083

AN:

5458

European-Non Finnish (NFE)

AF:

0.475

AC:

524237

AN:

1103686

Other (OTH)

AF:

0.503

AC:

30014

AN:

59638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

20045

40090

60136

80181

100226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15854

31708

47562

63416

79270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.426

AC:

64696

AN:

151992

Hom.:

15414

Cov.:

AF XY:

0.434

AC XY:

32212

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.227

AC:

9407

AN:

41484

American (AMR)

AF:

0.530

AC:

8101

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.548

AC:

1901

AN:

3472

East Asian (EAS)

AF:

0.727

AC:

3726

AN:

5126

South Asian (SAS)

AF:

0.774

AC:

3730

AN:

4820

European-Finnish (FIN)

AF:

0.406

AC:

4292

AN:

10576

Middle Eastern (MID)

AF:

0.503

AC:

147

AN:

292

European-Non Finnish (NFE)

AF:

0.474

AC:

32223

AN:

67912

Other (OTH)

AF:

0.460

AC:

972

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1778

3557

5335

7114

8892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

614

1228

1842

2456

3070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.463

Hom.:

66554

Bravo

AF:

0.422

Asia WGS

AF:

0.671

AC:

2333

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 29, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 03, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Retinitis pigmentosa 26

Benign:2

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 19, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Retinal dystrophy

Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Retinitis pigmentosa

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.94

PhyloP100

0.54

PromoterAI

0.018

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over