rs1441147

Variant names:

• chr2-181647129-T-C
• rs1441147
• NM_201548.5:c.238+9640A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201548.5(CERKL):​c.238+9640A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 152,008 control chromosomes in the GnomAD database, including 825 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 0.092 (825 hom., cov: 32)
• Consequence: CERKL NM_201548.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118
• Publications: 10 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERKL	NM_201548.5	c.238+9640A>G		intron_variant	Intron 1 of 12	ENST00000410087.8	NP_963842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERKL	ENST00000410087.8	c.238+9640A>G		intron_variant	Intron 1 of 12	1	NM_201548.5	ENSP00000386725.3

Frequencies

GnomAD3 genomes AF: 0.0920 AC: 13973 AN: 151890 Hom.: 824 Cov.: 32

Gnomad AFR AF: 0.0351

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0625

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.0553

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0817

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

GnomAD4 genome AF: 0.0921 AC: 14000 AN: 152008 Hom.: 825 Cov.: 32 AF XY: 0.0935 AC XY: 6949 AN XY: 74296

African (AFR) AF: 0.0354 AC: 1467 AN: 41470

American (AMR) AF: 0.0624 AC: 954 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0798 AC: 277 AN: 3470

East Asian (EAS) AF: 0.124 AC: 638 AN: 5156

South Asian (SAS) AF: 0.0564 AC: 271 AN: 4802

European-Finnish (FIN) AF: 0.176 AC: 1859 AN: 10576

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8241 AN: 67946

Other (OTH) AF: 0.0837 AC: 176 AN: 2104

Alfa AF: 0.107 Hom.: 811

Bravo AF: 0.0814

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.4
DANN	Benign	0.63
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1441147; hg19: chr2-182511856;