Genetic Variant CERKL:c.896-18T>A (chr2-181548875-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_201548.5(CERKL):c.896-18T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 1,607,236 control chromosomes in the GnomAD database, including 284,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27014 hom., cov: 32)

Exomes 𝑓: 0.59 ( 257089 hom. )

Consequence

CERKL
NM_201548.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.0370

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 2-181548875-A-T is Benign according to our data. Variant chr2-181548875-A-T is described in ClinVar as [Benign]. Clinvar id is 166846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-181548875-A-T is described in Lovd as [Benign].

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.896-18T>A		intron_variant	Intron 6 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.896-18T>A		intron_variant	Intron 6 of 12	1	NM_201548.5	ENSP00000386725.3		Q49MI3-2

Frequencies

GnomAD3 genomes

AF:

0.593

AC:

90133

AN:

151896

Hom.:

26999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.608

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.613

Gnomad ASJ

AF:

0.609

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.830

Gnomad FIN

AF:

0.505

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.575

Gnomad OTH

AF:

0.617

GnomAD3 exomes

AF:

0.611

AC:

152212

AN:

249028

Hom.:

47648

AF XY:

0.623

AC XY:

84046

AN XY:

134980

show subpopulations

Gnomad AFR exome

AF:

0.601

Gnomad AMR exome

AF:

0.603

Gnomad ASJ exome

AF:

0.602

Gnomad EAS exome

AF:

0.634

Gnomad SAS exome

AF:

0.834

Gnomad FIN exome

AF:

0.484

Gnomad NFE exome

AF:

0.576

Gnomad OTH exome

AF:

0.608

GnomAD4 exome

AF:

0.590

AC:

858167

AN:

1455222

Hom.:

257089

Cov.:

AF XY:

0.599

AC XY:

433683

AN XY:

724434

show subpopulations

Gnomad4 AFR exome

AF:

0.613

Gnomad4 AMR exome

AF:

0.604

Gnomad4 ASJ exome

AF:

0.611

Gnomad4 EAS exome

AF:

0.617

Gnomad4 SAS exome

AF:

0.836

Gnomad4 FIN exome

AF:

0.488

Gnomad4 NFE exome

AF:

0.571

Gnomad4 OTH exome

AF:

0.598

GnomAD4 genome

AF:

0.593

AC:

90203

AN:

152014

Hom.:

27014

Cov.:

AF XY:

0.595

AC XY:

44232

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.608

Gnomad4 AMR

AF:

0.613

Gnomad4 ASJ

AF:

0.609

Gnomad4 EAS

AF:

0.635

Gnomad4 SAS

AF:

0.830

Gnomad4 FIN

AF:

0.505

Gnomad4 NFE

AF:

0.575

Gnomad4 OTH

AF:

0.614

Alfa

AF:

0.587

Hom.:

4844

Bravo

AF:

0.596

Asia WGS

AF:

0.680

AC:

2365

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Apr 26, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

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

- -

Retinitis pigmentosa 26

Benign:3

May 31, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

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

- -

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

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

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Benign

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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