rs86337

chr22-50582239-C-Achr22-50582239-C-Gchr22-50582239-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005198.5(CHKB):c.333+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 1,572,346 control chromosomes in the GnomAD database, including 287,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (28352 hom., cov: 33)
  • Exomes 𝑓: 0.60 (259270 hom.)
• Consequence: CHKB NM_005198.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.920

Genes affected

CHKB (HGNC:1938): (choline kinase beta) Choline kinase (CK) and ethanolamine kinase (EK) catalyze the phosphorylation of choline/ethanolamine to phosphocholine/phosphoethanolamine. This is the first enzyme in the biosynthesis of phosphatidylcholine/phosphatidylethanolamine in all animal cells. The highly purified CKs from mammalian sources and their recombinant gene products have been shown to have EK activity also, indicating that both activities reside on the same protein. The choline kinase-like protein encoded by CHKL belongs to the choline/ethanolamine kinase family; however, its exact function is not known. Read-through transcripts are expressed from this locus that include exons from the downstream CPT1B locus. [provided by RefSeq, Jun 2009]

CHKB-CPT1B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 22-50582239-C-A is Benign according to our data. Variant chr22-50582239-C-A is described in ClinVar as [Benign]. Clinvar id is 128729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50582239-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHKB	NM_005198.5	c.333+10G>T		intron_variant		ENST00000406938.3
CHKB-CPT1B	NR_027928.2	n.551+10G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHKB	ENST00000406938.3	c.333+10G>T		intron_variant		1	NM_005198.5	P1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91830 AN: 151832 Hom.: 28317 Cov.: 33

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.582

GnomAD3 exomes AF: 0.657 AC: 124660 AN: 189754 Hom.: 42195 AF XY: 0.652 AC XY: 66628 AN XY: 102114

Gnomad AFR exome AF: 0.569

Gnomad AMR exome AF: 0.756

Gnomad ASJ exome AF: 0.582

Gnomad EAS exome AF: 0.974

Gnomad SAS exome AF: 0.696

Gnomad FIN exome AF: 0.651

Gnomad NFE exome AF: 0.578

Gnomad OTH exome AF: 0.617

GnomAD4 exome AF: 0.599 AC: 851162 AN: 1420396 Hom.: 259270 Cov.: 32 AF XY: 0.601 AC XY: 422784 AN XY: 703334

Gnomad4 AFR exome AF: 0.575

Gnomad4 AMR exome AF: 0.746

Gnomad4 ASJ exome AF: 0.578

Gnomad4 EAS exome AF: 0.960

Gnomad4 SAS exome AF: 0.697

Gnomad4 FIN exome AF: 0.642

Gnomad4 NFE exome AF: 0.574

Gnomad4 OTH exome AF: 0.601

GnomAD4 genome AF: 0.605 AC: 91921 AN: 151950 Hom.: 28352 Cov.: 33 AF XY: 0.614 AC XY: 45628 AN XY: 74268

Gnomad4 AFR AF: 0.568

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.970

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.588

Alfa AF: 0.551 Hom.: 7759

Bravo AF: 0.607

Asia WGS AF: 0.840 AC: 2920 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Megaconial type congenital muscular dystrophy Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	7.2
Dann	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs86337; hg19: chr22-51020668;