22-46726863-C-G

Variant names:

• chr22-46726863-C-G
• rs5769116
• NM_022766.6:c.143-5848G>C

Variant summary

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

The NM_022766.6(CERK):​c.143-5848G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,856 control chromosomes in the GnomAD database, including 17,325 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 0.45 (17325 hom., cov: 31)
• Consequence: CERK NM_022766.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 2 publications found

Genes affected

CERK (HGNC:19256): (ceramide kinase) CERK converts ceramide to ceramide 1-phosphate (C1P), a sphingolipid metabolite. Both CERK and C1P have been implicated in various cellular processes, including proliferation, apoptosis, phagocytosis, and inflammation (Kim et al., 2006 [PubMed 16488390]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERK	NM_022766.6	c.143-5848G>C		intron_variant	Intron 1 of 12	ENST00000216264.13	NP_073603.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERK	ENST00000216264.13	c.143-5848G>C		intron_variant	Intron 1 of 12	1	NM_022766.6	ENSP00000216264.8
CERK	ENST00000443629.5	n.143-5848G>C		intron_variant	Intron 1 of 11	1		ENSP00000400859.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67763 AN: 151738 Hom.: 17333 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.446 AC: 67761 AN: 151856 Hom.: 17325 Cov.: 31 AF XY: 0.446 AC XY: 33071 AN XY: 74194

African (AFR) AF: 0.175 AC: 7236 AN: 41444

American (AMR) AF: 0.512 AC: 7800 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1924 AN: 3472

East Asian (EAS) AF: 0.502 AC: 2568 AN: 5112

South Asian (SAS) AF: 0.504 AC: 2427 AN: 4812

European-Finnish (FIN) AF: 0.551 AC: 5803 AN: 10534

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38322 AN: 67934

Other (OTH) AF: 0.491 AC: 1036 AN: 2108

Alfa AF: 0.494 Hom.: 2509

Bravo AF: 0.430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.42
PhyloP100		0.056
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs5769116; hg19: chr22-47122760;