NM_201548.5:c.156C>T

Variant names:

• chr2-181656851-G-A
• rs1473295
• NM_201548.5:c.156C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_201548.5(CERKL):​c.156C>T​(p.Phe52Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,601,126 control chromosomes in the GnomAD database, including 202,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15414 hom., cov: 32)
  • Exomes 𝑓: 0.50 (186674 hom.)
• Consequence: CERKL NM_201548.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 0.539
• Publications: 21 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 2-181656851-G-A is Benign according to our data. Variant chr2-181656851-G-A is described in ClinVar as Benign. ClinVar VariationId is 166849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.539 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.753 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.156C>T	p.Phe52Phe	synonymous	Exon 1 of 13	NP_963842.1	Q49MI3-2
	CERKL	NM_001030311.3		c.156C>T	p.Phe52Phe	synonymous	Exon 1 of 14	NP_001025482.1	Q49MI3-1
	CERKL	NM_001160277.2		c.156C>T	p.Phe52Phe	synonymous	Exon 1 of 13	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.156C>T	p.Phe52Phe	synonymous	Exon 1 of 13	ENSP00000386725.3	Q49MI3-2
	CERKL	ENST00000339098.9	TSL:1	c.156C>T	p.Phe52Phe	synonymous	Exon 1 of 14	ENSP00000341159.5	Q49MI3-1
	CERKL	ENST00000374970.6	TSL:1	c.156C>T	p.Phe52Phe	synonymous	Exon 1 of 11	ENSP00000364109.2	Q49MI3-3

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64701 AN: 151874 Hom.: 15429 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.463

GnomAD2 exomes AF: 0.528 AC: 126651 AN: 240042 AF XY: 0.540

Gnomad AFR exome AF: 0.227

Gnomad AMR exome AF: 0.608

Gnomad ASJ exome AF: 0.534

Gnomad EAS exome AF: 0.711

Gnomad FIN exome AF: 0.394

Gnomad NFE exome AF: 0.468

Gnomad OTH exome AF: 0.510

GnomAD4 exome AF: 0.498 AC: 721361 AN: 1449134 Hom.: 186674 Cov.: 58 AF XY: 0.507 AC XY: 364263 AN XY: 718744

African (AFR) AF: 0.221 AC: 7248 AN: 32824

American (AMR) AF: 0.600 AC: 26596 AN: 44322

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 13983 AN: 25892

East Asian (EAS) AF: 0.729 AC: 28415 AN: 39004

South Asian (SAS) AF: 0.783 AC: 66953 AN: 85504

European-Finnish (FIN) AF: 0.395 AC: 20832 AN: 52806

Middle Eastern (MID) AF: 0.565 AC: 3083 AN: 5458

European-Non Finnish (NFE) AF: 0.475 AC: 524237 AN: 1103686

Other (OTH) AF: 0.503 AC: 30014 AN: 59638

GnomAD4 genome AF: 0.426 AC: 64696 AN: 151992 Hom.: 15414 Cov.: 32 AF XY: 0.434 AC XY: 32212 AN XY: 74300

African (AFR) AF: 0.227 AC: 9407 AN: 41484

American (AMR) AF: 0.530 AC: 8101 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1901 AN: 3472

East Asian (EAS) AF: 0.727 AC: 3726 AN: 5126

South Asian (SAS) AF: 0.774 AC: 3730 AN: 4820

European-Finnish (FIN) AF: 0.406 AC: 4292 AN: 10576

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.474 AC: 32223 AN: 67912

Other (OTH) AF: 0.460 AC: 972 AN: 2114

Alfa AF: 0.463 Hom.: 66554

Bravo AF: 0.422

Asia WGS AF: 0.671 AC: 2333 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	not provided (3)
-	-	2	Retinitis pigmentosa 26 (2)
-	-	1	Retinal dystrophy (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	11
DANN	Benign	0.94
PhyloP100		0.54
PromoterAI		0.018	Neutral
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: rs1473295; hg19: chr2-182521578; COSMIC: COSV59207888;