rs10180793
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_201548.5(CERKL):c.1506C>T(p.Asp502=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,608,470 control chromosomes in the GnomAD database, including 801,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.99 ( 75051 hom., cov: 31)
Exomes 𝑓: 1.0 ( 726860 hom. )
Consequence
CERKL
NM_201548.5 synonymous
NM_201548.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.749
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 2-181539124-G-A is Benign according to our data. Variant chr2-181539124-G-A is described in ClinVar as [Benign]. Clinvar id is 166844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-181539124-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.749 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CERKL | NM_201548.5 | c.1506C>T | p.Asp502= | synonymous_variant | 12/13 | ENST00000410087.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CERKL | ENST00000410087.8 | c.1506C>T | p.Asp502= | synonymous_variant | 12/13 | 1 | NM_201548.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.993 AC: 151050AN: 152134Hom.: 75001 Cov.: 31
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GnomAD3 exomes AF: 0.998 AC: 250751AN: 251272Hom.: 125119 AF XY: 0.998 AC XY: 135604AN XY: 135808
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GnomAD4 exome AF: 0.999 AC: 1454956AN: 1456218Hom.: 726860 Cov.: 38 AF XY: 0.999 AC XY: 724216AN XY: 724762
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GnomAD4 genome ? AF: 0.993 AC: 151159AN: 152252Hom.: 75051 Cov.: 31 AF XY: 0.993 AC XY: 73902AN XY: 74436
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
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, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 19, 2014 | - - |
Retinitis pigmentosa 26 Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 21, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
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 | - - |
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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at