Variant 22-46690151-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_022766.6(CERK):c.1382C>T(p.Thr461Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000726 in 1,613,972 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 4 hom., cov: 31)

Exomes 𝑓: 0.00038 ( 2 hom. )

Consequence

CERK
NM_022766.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.18

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010273844).

BP6

Variant 22-46690151-G-A is Benign according to our data. Variant chr22-46690151-G-A is described in ClinVar as [Benign]. Clinvar id is 731194.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERK	NM_022766.6 linkuse as main transcript	c.1382C>T	p.Thr461Met	missense_variant	12/13	ENST00000216264.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERK	ENST00000216264.13 linkuse as main transcript	c.1382C>T	p.Thr461Met	missense_variant	12/13	1	NM_022766.6	P1	Q8TCT0-1
CERK	ENST00000443629.5 linkuse as main transcript	c.*760C>T		3_prime_UTR_variant, NMD_transcript_variant	11/12	1
CERK	ENST00000471929.1 linkuse as main transcript	n.471C>T		non_coding_transcript_exon_variant	4/4	4

Frequencies

GnomAD3 genomes

AF:

0.00405

AC:

616

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00103

AC:

259

AN:

251470

Hom.:

AF XY:

0.000714

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.000520

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000380

AC:

555

AN:

1461852

Hom.:

Cov.:

AF XY:

0.000329

AC XY:

239

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0134

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.000993

GnomAD4 genome

AF:

0.00405

AC:

616

AN:

152120

Hom.:

Cov.:

AF XY:

0.00383

AC XY:

285

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0141

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.000736

Hom.:

Bravo

AF:

0.00451

ESP6500AA

AF:

0.0125

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00121

AC:

147

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.28

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.74

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.1

REVEL

Benign

0.058

Sift

Benign

0.12

Sift4G

Benign

0.077

Polyphen

0.61

Vest4

0.22

MVP

0.35

MPC

0.22

ClinPred

0.0082

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.028

gMVP

0.39

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over