dbSNP rs36211083: CERK:p.Asp377Asp (chr22-46691773-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_022766.6(CERK):c.1131C>T(p.Asp377Asp) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.49

Publications

11 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 -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 rank	MANE	Protein	UniProt
CERK	NM_022766.6 link	c.1131C>T	p.Asp377Asp	synonymous_variant	Exon 11 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.1131C>T	p.Asp377Asp	synonymous_variant	Exon 11 of 13	1	NM_022766.6	ENSP00000216264.8	Q8TCT0-1
CERK	ENST00000443629.5 link	n.*509C>T		non_coding_transcript_exon_variant	Exon 10 of 12	1		ENSP00000400859.1	F8WFD8
CERK	ENST00000443629.5 link	n.*509C>T		3_prime_UTR_variant	Exon 10 of 12	1		ENSP00000400859.1	F8WFD8
CERK	ENST00000471929.1 link	n.220C>T		non_coding_transcript_exon_variant	Exon 3 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17702

AN:

152140

Hom.:

1119

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.119

AC:

29636

AN:

248854

AF XY:

0.114

show subpopulations

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 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.:

AF XY:

0.113

AC XY:

81635

AN XY:

722634

show subpopulations

African (AFR)

AF:

0.123

AC:

4088

AN:

33342

American (AMR)

AF:

0.232

AC:

10318

AN:

44482

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

2880

AN:

26058

East Asian (EAS)

AF:

0.00253

AC:

100

AN:

39548

South Asian (SAS)

AF:

0.0885

AC:

7612

AN:

86058

European-Finnish (FIN)

AF:

0.0846

AC:

4507

AN:

53246

Middle Eastern (MID)

AF:

0.112

AC:

610

AN:

5426

European-Non Finnish (NFE)

AF:

0.117

AC:

129315

AN:

1106644

Other (OTH)

AF:

0.106

AC:

6371

AN:

60080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

6292

12583

18875

25166

31458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4752

9504

14256

19008

23760

<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:

0.116

AC:

17719

AN:

152258

Hom.:

1123

Cov.:

AF XY:

0.115

AC XY:

8557

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.124

AC:

5172

AN:

41550

American (AMR)

AF:

0.173

AC:

2650

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

414

AN:

3472

East Asian (EAS)

AF:

0.00309

AC:

AN:

5184

South Asian (SAS)

AF:

0.0838

AC:

405

AN:

4832

European-Finnish (FIN)

AF:

0.0844

AC:

895

AN:

10608

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.116

AC:

7885

AN:

68010

Other (OTH)

AF:

0.104

AC:

221

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

829

1658

2486

3315

4144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<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:

0.122

Hom.:

1053

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

(source)

DANN

Benign

0.61

PhyloP100

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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