NM_201548.5:c.1133+13T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_201548.5(CERKL):c.1133+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 1,568,092 control chromosomes in the GnomAD database, including 276,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27050 hom., cov: 32)

Exomes 𝑓: 0.59 ( 249734 hom. )

Consequence

CERKL
NM_201548.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.323

Publications

25 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 2-181548532-A-G is Benign according to our data. Variant chr2-181548532-A-G is described in ClinVar as Benign. ClinVar VariationId is 257149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERKL	NM_201548.5 link	c.1133+13T>C		intron_variant	Intron 8 of 12	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.1133+13T>C		intron_variant	Intron 8 of 12	1	NM_201548.5	ENSP00000386725.3		Q49MI3-2

Frequencies

GnomAD3 genomes

AF:

0.594

AC:

90208

AN:

151896

Hom.:

27035

Cov.:

show subpopulations

Gnomad AFR

AF:

0.608

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.612

Gnomad ASJ

AF:

0.609

Gnomad EAS

AF:

0.632

Gnomad SAS

AF:

0.830

Gnomad FIN

AF:

0.506

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.576

Gnomad OTH

AF:

0.618

GnomAD2 exomes

AF:

0.610

AC:

149855

AN:

245500

AF XY:

0.622

show subpopulations

Gnomad AFR exome

AF:

0.600

Gnomad AMR exome

AF:

0.602

Gnomad ASJ exome

AF:

0.602

Gnomad EAS exome

AF:

0.633

Gnomad FIN exome

AF:

0.484

Gnomad NFE exome

AF:

0.575

Gnomad OTH exome

AF:

0.607

GnomAD4 exome

AF:

0.589

AC:

833933

AN:

1416078

Hom.:

249734

Cov.:

AF XY:

0.598

AC XY:

422966

AN XY:

707022

show subpopulations

African (AFR)

AF:

0.611

AC:

19889

AN:

32544

American (AMR)

AF:

0.603

AC:

26628

AN:

44156

Ashkenazi Jewish (ASJ)

AF:

0.611

AC:

15776

AN:

25832

East Asian (EAS)

AF:

0.616

AC:

24191

AN:

39276

South Asian (SAS)

AF:

0.836

AC:

71005

AN:

84900

European-Finnish (FIN)

AF:

0.489

AC:

25970

AN:

53128

Middle Eastern (MID)

AF:

0.716

AC:

4058

AN:

5664

European-Non Finnish (NFE)

AF:

0.570

AC:

611337

AN:

1071880

Other (OTH)

AF:

0.598

AC:

35079

AN:

58698

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

15762

31523

47285

63046

78808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16836

33672

50508

67344

84180

<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:

0.594

AC:

90278

AN:

152014

Hom.:

27050

Cov.:

AF XY:

0.596

AC XY:

44289

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.608

AC:

25165

AN:

41422

American (AMR)

AF:

0.613

AC:

9358

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.609

AC:

2113

AN:

3470

East Asian (EAS)

AF:

0.633

AC:

3275

AN:

5174

South Asian (SAS)

AF:

0.830

AC:

4001

AN:

4820

European-Finnish (FIN)

AF:

0.506

AC:

5347

AN:

10568

Middle Eastern (MID)

AF:

0.663

AC:

195

AN:

294

European-Non Finnish (NFE)

AF:

0.576

AC:

39177

AN:

67976

Other (OTH)

AF:

0.614

AC:

1298

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1929

3858

5788

7717

9646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.583

Hom.:

41968

Bravo

AF:

0.596

Asia WGS

AF:

0.680

AC:

2365

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

Retinitis pigmentosa 26

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.83

CADD

Benign

3.7

(source)

DANN

Benign

0.43

PhyloP100

0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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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