22-46726863-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CERK	NM_022766.6	c.143-5848G>C		intron_variant		ENST00000216264.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERK	ENST00000216264.13	c.143-5848G>C		intron_variant		1	NM_022766.6	P1
CERK	ENST00000443629.5	c.143-5848G>C		intron_variant, NMD_transcript_variant		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

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.491

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs5769116; hg19: chr22-47122760;