rs34110809

Variant names:

• chr22-46690006-A-T
• rs34110809
• NM_022766.6:c.1527T>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_022766.6(CERK):​c.1527T>A​(p.Pro509Pro) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.97
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.1).
• BP6: Variant 22-46690006-A-T is Benign according to our data. Variant chr22-46690006-A-T is described in ClinVar as Benign. ClinVar VariationId is 777761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.97 with no splicing effect.
• BS1: 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 40 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022766.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERK	NM_022766.6	MANE Select	c.1527T>A	p.Pro509Pro	synonymous	Exon 12 of 13	NP_073603.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERK	ENST00000216264.13	TSL:1 MANE Select	c.1527T>A	p.Pro509Pro	synonymous	Exon 12 of 13	ENSP00000216264.8	Q8TCT0-1
	CERK	ENST00000443629.5	TSL:1	n.*905T>A		non_coding_transcript_exon	Exon 11 of 12	ENSP00000400859.1	F8WFD8
	CERK	ENST00000443629.5	TSL:1	n.*905T>A		3_prime_UTR	Exon 11 of 12	ENSP00000400859.1	F8WFD8

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1904 AN: 151890 Hom.: 40 Cov.: 32

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

GnomAD2 exomes AF: 0.00354 AC: 860 AN: 242930 AF XY: 0.00264

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 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

African (AFR) AF: 0.0472 AC: 1578 AN: 33466

American (AMR) AF: 0.00254 AC: 113 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26036

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86050

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47838

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5754

European-Non Finnish (NFE) AF: 0.000145 AC: 161 AN: 1111564

Other (OTH) AF: 0.00337 AC: 203 AN: 60302

GnomAD4 genome AF: 0.0126 AC: 1910 AN: 152008 Hom.: 40 Cov.: 32 AF XY: 0.0123 AC XY: 911 AN XY: 74332

African (AFR) AF: 0.0436 AC: 1806 AN: 41436

American (AMR) AF: 0.00439 AC: 67 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67958

Other (OTH) AF: 0.00852 AC: 18 AN: 2112

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.021
DANN	Benign	0.27
PhyloP100		-4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs34110809; hg19: chr22-47085903;