Menu
GeneBe

22-46690006-A-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_022766.6(CERK):c.1527T>A(p.Pro509=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,607,210 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 40 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 44 hom. )

Consequence

CERK
NM_022766.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.97
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-1.1).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-46690006-A-T is Benign according to our data. Variant chr22-46690006-A-T is described in ClinVar as [Benign]. Clinvar id is 777761.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.97 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1910/152008) while in subpopulation AFR AF= 0.0436 (1806/41436). AF 95% confidence interval is 0.0419. There are 40 homozygotes in gnomad4. There are 911 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 40 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CERKNM_022766.6 linkuse as main transcriptc.1527T>A p.Pro509= synonymous_variant 12/13 ENST00000216264.13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CERKENST00000216264.13 linkuse as main transcriptc.1527T>A p.Pro509= synonymous_variant 12/131 NM_022766.6 P1Q8TCT0-1
CERKENST00000443629.5 linkuse as main transcriptc.*905T>A 3_prime_UTR_variant, NMD_transcript_variant 11/121
CERKENST00000471929.1 linkuse as main transcript downstream_gene_variant 4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0125
AC:
1904
AN:
151890
Hom.:
40
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0435
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00439
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.00861
GnomAD3 exomes
AF:
0.00354
AC:
860
AN:
242930
Hom.:
17
AF XY:
0.00264
AC XY:
350
AN XY:
132476
show subpopulations
Gnomad AFR exome
AF:
0.0476
Gnomad AMR exome
AF:
0.00237
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000658
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000225
Gnomad OTH exome
AF:
0.00167
GnomAD4 exome
AF:
0.00143
AC:
2085
AN:
1455202
Hom.:
44
Cov.:
31
AF XY:
0.00120
AC XY:
872
AN XY:
724202
show subpopulations
Gnomad4 AFR exome
AF:
0.0472
Gnomad4 AMR exome
AF:
0.00254
Gnomad4 ASJ exome
AF:
0.0000384
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000145
Gnomad4 OTH exome
AF:
0.00337
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0126
AC:
1910
AN:
152008
Hom.:
40
Cov.:
32
AF XY:
0.0123
AC XY:
911
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.0436
Gnomad4 AMR
AF:
0.00439
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.00852
Alfa
AF:
0.00499
Hom.:
4
Bravo
AF:
0.0143
Asia WGS
AF:
0.00375
AC:
14
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.000298

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 submitterclinical testingInvitaeJun 21, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.1
Cadd
Benign
0.021
Dann
Benign
0.27
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs34110809; hg19: chr22-47085903; API