Genetic Variant CERK:p.Thr211Met (chr22-46707926-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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.

Frequency

Genomes: 𝑓 0.014 ( 40 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 42 hom. )

Consequence

CERK
NM_022766.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.98

Publications

7 publications found

Variant links:

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]

CERK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERK	NM_022766.6 link	c.632C>T	p.Thr211Met	missense_variant	Exon 6 of 13	ENST00000216264.13	NP_073603.2	Q8TCT0-1A0A024R4U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CERK	ENST00000216264.13 link	c.632C>T	p.Thr211Met	missense_variant	Exon 6 of 13	1	NM_022766.6	ENSP00000216264.8	Q8TCT0-1
CERK	ENST00000443629.5 link	n.*10C>T		non_coding_transcript_exon_variant	Exon 5 of 12	1		ENSP00000400859.1	F8WFD8
CERK	ENST00000443629.5 link	n.*10C>T		3_prime_UTR_variant	Exon 5 of 12	1		ENSP00000400859.1	F8WFD8

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

2068

AN:

152092

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00326

AC:

819

AN:

250970

AF XY:

0.00226

show subpopulations

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 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.:

Cov.:

AF XY:

0.00111

AC XY:

810

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.0455

AC:

1524

AN:

33478

American (AMR)

AF:

0.00215

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000220

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53200

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000459

AC:

AN:

1111962

Other (OTH)

AF:

0.00272

AC:

164

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

187

280

374

467

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0136

AC:

2074

AN:

152210

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

1035

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0477

AC:

1982

AN:

41516

American (AMR)

AF:

0.00405

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68012

Other (OTH)

AF:

0.00898

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

193

289

386

482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00360

Hom.:

Bravo

AF:

0.0147

ESP6500AA

AF:

0.0463

AC:

204

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00412

AC:

500

Asia WGS

AF:

0.00202

AC:

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

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.0053

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

4.0

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.086

Sift

Benign

0.075

Sift4G

Benign

0.12

Polyphen

0.88

Vest4

0.21

MVP

0.32

MPC

0.52

ClinPred

0.028

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.067

gMVP

0.47

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over