rs16867464

Variant names:

• chr2-181631738-C-T
• rs16867464
• NM_201548.5:c.238+25031G>A

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+25031G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,170 control chromosomes in the GnomAD database, including 1,325 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 0.11 (1325 hom., cov: 32)
• Consequence: CERKL NM_201548.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201548.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERKL	NM_201548.5	MANE Select	c.238+25031G>A		intron	N/A	NP_963842.1	Q49MI3-2
	CERKL	NM_001030311.3		c.238+25031G>A		intron	N/A	NP_001025482.1	Q49MI3-1
	CERKL	NM_001160277.2		c.238+25031G>A		intron	N/A	NP_001153749.1	Q49MI3-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERKL	ENST00000410087.8	TSL:1 MANE Select	c.238+25031G>A		intron	N/A	ENSP00000386725.3	Q49MI3-2
	CERKL	ENST00000339098.9	TSL:1	c.238+25031G>A		intron	N/A	ENSP00000341159.5	Q49MI3-1
	CERKL	ENST00000374970.6	TSL:1	c.238+25031G>A		intron	N/A	ENSP00000364109.2	Q49MI3-3

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17169 AN: 152052 Hom.: 1322 Cov.: 32

Gnomad AFR AF: 0.0306

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0770

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.0610

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.0945

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

GnomAD4 genome AF: 0.113 AC: 17179 AN: 152170 Hom.: 1325 Cov.: 32 AF XY: 0.119 AC XY: 8823 AN XY: 74372

African (AFR) AF: 0.0307 AC: 1276 AN: 41566

American (AMR) AF: 0.167 AC: 2549 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0770 AC: 267 AN: 3468

East Asian (EAS) AF: 0.217 AC: 1120 AN: 5162

South Asian (SAS) AF: 0.0613 AC: 296 AN: 4832

European-Finnish (FIN) AF: 0.216 AC: 2286 AN: 10562

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9145 AN: 67994

Other (OTH) AF: 0.0969 AC: 204 AN: 2106

Alfa AF: 0.125 Hom.: 712

Bravo AF: 0.106

Asia WGS AF: 0.164 AC: 569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.46
PhyloP100		-0.018
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: rs16867464; hg19: chr2-182496465;