22-46691773-G-A

Position:

• chr22-46691773-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_022766.6(CERK):​c.1131C>T​(p.Asp377=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,607,142 control chromosomes in the GnomAD database, including 11,413 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 0.12 (1123 hom., cov: 33)
  • Exomes 𝑓: 0.11 (10290 hom.)
• Consequence: CERK NM_022766.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-1.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERK	NM_022766.6	c.1131C>T	p.Asp377=	synonymous_variant	11/13	ENST00000216264.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERK	ENST00000216264.13	c.1131C>T	p.Asp377=	synonymous_variant	11/13	1	NM_022766.6	P1
CERK	ENST00000443629.5	c.*509C>T		3_prime_UTR_variant, NMD_transcript_variant	10/12	1
CERK	ENST00000471929.1	n.220C>T		non_coding_transcript_exon_variant	3/4	4

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17702 AN: 152140 Hom.: 1119 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0842

Gnomad FIN AF: 0.0844

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.106

GnomAD3 exomes AF: 0.119 AC: 29636 AN: 248854 Hom.: 2277 AF XY: 0.114 AC XY: 15307 AN XY: 134814

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.246

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.00240

Gnomad SAS exome AF: 0.0856

Gnomad FIN exome AF: 0.0809

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.107

GnomAD4 exome AF: 0.114 AC: 165801 AN: 1454884 Hom.: 10290 Cov.: 32 AF XY: 0.113 AC XY: 81635 AN XY: 722634

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.00253

Gnomad4 SAS exome AF: 0.0885

Gnomad4 FIN exome AF: 0.0846

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.116 AC: 17719 AN: 152258 Hom.: 1123 Cov.: 33 AF XY: 0.115 AC XY: 8557 AN XY: 74438

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0838

Gnomad4 FIN AF: 0.0844

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.104

Alfa AF: 0.122 Hom.: 823

Bravo AF: 0.123

Asia WGS AF: 0.0480 AC: 167 AN: 3478

EpiCase AF: 0.115

EpiControl AF: 0.108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs36211083; hg19: chr22-47087670; COSMIC: COSV53454010;