rs12997453

Variant names:

• chr2-181548532-A-G
• rs12997453
• NM_201548.5:c.1133+13T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-181548532-A-G
• chr2-181548532-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_201548.5(CERKL):​c.1133+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 1,568,092 control chromosomes in the GnomAD database, including 276,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (27050 hom., cov: 32)
  • Exomes 𝑓: 0.59 (249734 hom.)
• Consequence: CERKL NM_201548.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.323
• Publications: 25 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-181548532-A-G is Benign according to our data. Variant chr2-181548532-A-G is described in ClinVar as Benign. ClinVar VariationId is 257149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.809 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.1133+13T>C		intron	N/A	NP_963842.1	Q49MI3-2
	CERKL	NM_001030311.3		c.1211+13T>C		intron	N/A	NP_001025482.1	Q49MI3-1
	CERKL	NM_001160277.2		c.1079+13T>C		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.1133+13T>C		intron	N/A	ENSP00000386725.3	Q49MI3-2
	CERKL	ENST00000339098.9	TSL:1	c.1211+13T>C		intron	N/A	ENSP00000341159.5	Q49MI3-1
	CERKL	ENST00000374970.6	TSL:1	c.926+13T>C		intron	N/A	ENSP00000364109.2	Q49MI3-3

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90208 AN: 151896 Hom.: 27035 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.618

GnomAD2 exomes AF: 0.610 AC: 149855 AN: 245500 AF XY: 0.622

Gnomad AFR exome AF: 0.600

Gnomad AMR exome AF: 0.602

Gnomad ASJ exome AF: 0.602

Gnomad EAS exome AF: 0.633

Gnomad FIN exome AF: 0.484

Gnomad NFE exome AF: 0.575

Gnomad OTH exome AF: 0.607

GnomAD4 exome AF: 0.589 AC: 833933 AN: 1416078 Hom.: 249734 Cov.: 25 AF XY: 0.598 AC XY: 422966 AN XY: 707022

African (AFR) AF: 0.611 AC: 19889 AN: 32544

American (AMR) AF: 0.603 AC: 26628 AN: 44156

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 15776 AN: 25832

East Asian (EAS) AF: 0.616 AC: 24191 AN: 39276

South Asian (SAS) AF: 0.836 AC: 71005 AN: 84900

European-Finnish (FIN) AF: 0.489 AC: 25970 AN: 53128

Middle Eastern (MID) AF: 0.716 AC: 4058 AN: 5664

European-Non Finnish (NFE) AF: 0.570 AC: 611337 AN: 1071880

Other (OTH) AF: 0.598 AC: 35079 AN: 58698

GnomAD4 genome AF: 0.594 AC: 90278 AN: 152014 Hom.: 27050 Cov.: 32 AF XY: 0.596 AC XY: 44289 AN XY: 74306

African (AFR) AF: 0.608 AC: 25165 AN: 41422

American (AMR) AF: 0.613 AC: 9358 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2113 AN: 3470

East Asian (EAS) AF: 0.633 AC: 3275 AN: 5174

South Asian (SAS) AF: 0.830 AC: 4001 AN: 4820

European-Finnish (FIN) AF: 0.506 AC: 5347 AN: 10568

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39177 AN: 67976

Other (OTH) AF: 0.614 AC: 1298 AN: 2114

Alfa AF: 0.583 Hom.: 41968

Bravo AF: 0.596

Asia WGS AF: 0.680 AC: 2365 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Retinitis pigmentosa (1)
-	-	1	Retinitis pigmentosa 26 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.43
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12997453; hg19: chr2-182413259; COSMIC: COSV59207851;