rs993648

chr2-181591267-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201548.5(CERKL):c.481+12570G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,776 control chromosomes in the GnomAD database, including 13,596 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (13596 hom., cov: 31)
• Consequence: CERKL NM_201548.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERKL	NM_201548.5	c.481+12570G>A		intron_variant		ENST00000410087.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERKL	ENST00000410087.8	c.481+12570G>A		intron_variant		1	NM_201548.5	P1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56032 AN: 151658 Hom.: 13565 Cov.: 31

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.0628

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.370 AC: 56123 AN: 151776 Hom.: 13596 Cov.: 31 AF XY: 0.374 AC XY: 27701 AN XY: 74118

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.307

Alfa AF: 0.235 Hom.: 9384

Bravo AF: 0.388

Asia WGS AF: 0.312 AC: 1085 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.5
Dann	Benign	0.29

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

Other links and lift over

dbSNP: rs993648; hg19: chr2-182455994;