rs9306515

chr22-46707926-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_022766.6(CERK):c.632C>T(p.Thr211Met) variant causes a missense change. The variant allele was found at a frequency of 0.00244 in 1,613,812 control chromosomes in the GnomAD database, including 82 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.014 (40 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (42 hom.)
• Consequence: CERK NM_022766.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98

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 (MetaRNN=0.0053140223).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0136 (2074/152210) while in subpopulation AFR AF= 0.0477 (1982/41516). AF 95% confidence interval is 0.046. There are 40 homozygotes in gnomad4. There are 1035 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERK	NM_022766.6	c.632C>T	p.Thr211Met	missense_variant	6/13	ENST00000216264.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERK	ENST00000216264.13	c.632C>T	p.Thr211Met	missense_variant	6/13	1	NM_022766.6	P1
CERK	ENST00000443629.5	c.*10C>T		3_prime_UTR_variant, NMD_transcript_variant	5/12	1

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2068 AN: 152092 Hom.: 39 Cov.: 33

Gnomad AFR AF: 0.0477

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00907

GnomAD3 exomes AF: 0.00326 AC: 819 AN: 250970 Hom.: 14 AF XY: 0.00226 AC XY: 307 AN XY: 135696

Gnomad AFR exome AF: 0.0452

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00128 AC: 1869 AN: 1461602 Hom.: 42 Cov.: 31 AF XY: 0.00111 AC XY: 810 AN XY: 727120

Gnomad4 AFR exome AF: 0.0455

Gnomad4 AMR exome AF: 0.00215

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000220

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000459

Gnomad4 OTH exome AF: 0.00272

GnomAD4 genome AF: 0.0136 AC: 2074 AN: 152210 Hom.: 40 Cov.: 33 AF XY: 0.0139 AC XY: 1035 AN XY: 74418

Gnomad4 AFR AF: 0.0477

Gnomad4 AMR AF: 0.00405

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00240 Hom.: 24

Bravo AF: 0.0147

ESP6500AA AF: 0.0463 AC: 204

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00412 AC: 500

Asia WGS AF: 0.00202 AC: 8 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0053	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.086
Sift	Benign	0.075	T
Sift4G	Benign	0.12	T
Polyphen		0.88	P
Vest4		0.21
MVP		0.32
MPC		0.52
ClinPred		0.028	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.067
gMVP		0.47

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: rs9306515; hg19: chr22-47103823;