dbSNP rs9616098: CERK:c.944-19C>T (chr22-46695334-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.944-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 1,413,760 control chromosomes in the GnomAD database, including 285 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.013 ( 16 hom., cov: 33)

Exomes 𝑓: 0.018 ( 269 hom. )

Consequence

CERK
NM_022766.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.685

Publications

4 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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0129 (1962/152330) while in subpopulation SAS AF = 0.0288 (139/4830). AF 95% confidence interval is 0.0249. There are 16 homozygotes in GnomAd4. There are 984 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERK	NM_022766.6 link	c.944-19C>T		intron_variant	Intron 8 of 12	ENST00000216264.13	NP_073603.2	Q8TCT0-1A0A024R4U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERK	ENST00000216264.13 link	c.944-19C>T		intron_variant	Intron 8 of 12	1	NM_022766.6	ENSP00000216264.8		Q8TCT0-1
CERK	ENST00000443629.5 link	n.*322-19C>T		intron_variant	Intron 7 of 11	1		ENSP00000400859.1		F8WFD8

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1964

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00374

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0292

Gnomad FIN

AF:

0.0213

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0188

Gnomad OTH

AF:

0.00764

GnomAD2 exomes

AF:

0.0153

AC:

3841

AN:

250962

AF XY:

0.0168

show subpopulations

Gnomad AFR exome

AF:

0.00252

Gnomad AMR exome

AF:

0.00538

Gnomad ASJ exome

AF:

0.00943

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0189

Gnomad NFE exome

AF:

0.0188

Gnomad OTH exome

AF:

0.0136

GnomAD4 exome

AF:

0.0177

AC:

22359

AN:

1261430

Hom.:

269

Cov.:

AF XY:

0.0184

AC XY:

11762

AN XY:

637968

show subpopulations

African (AFR)

AF:

0.00303

AC:

AN:

29416

American (AMR)

AF:

0.00544

AC:

242

AN:

44454

Ashkenazi Jewish (ASJ)

AF:

0.00916

AC:

228

AN:

24888

East Asian (EAS)

AF:

0.000516

AC:

AN:

38786

South Asian (SAS)

AF:

0.0299

AC:

2458

AN:

82246

European-Finnish (FIN)

AF:

0.0211

AC:

1118

AN:

53070

Middle Eastern (MID)

AF:

0.0121

AC:

AN:

5380

European-Non Finnish (NFE)

AF:

0.0186

AC:

17321

AN:

929366

Other (OTH)

AF:

0.0152

AC:

818

AN:

53824

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

949

1897

2846

3794

4743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

612

1224

1836

2448

3060

<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:

0.0129

AC:

1962

AN:

152330

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

984

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00373

AC:

155

AN:

41592

American (AMR)

AF:

0.00686

AC:

105

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

AN:

3472

East Asian (EAS)

AF:

0.000772

AC:

AN:

5184

South Asian (SAS)

AF:

0.0288

AC:

139

AN:

4830

European-Finnish (FIN)

AF:

0.0213

AC:

226

AN:

10612

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0188

AC:

1276

AN:

68018

Other (OTH)

AF:

0.00756

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

106

212

319

425

531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0158

Hom.:

Bravo

AF:

0.0111

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.17

(source)

DANN

Benign

0.33

PhyloP100

-0.69

BranchPoint Hunter

3.0

Mutation Taster

=100/0

polymorphism (auto)

(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