chr22-50582239-C-A

Variant names:

• chr22-50582239-C-A
• rs86337
• ENST00000481673.5:n.407G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000481673.5(CHKB):​n.407G>T variant causes a non coding transcript exon 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 ENST00000481673.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.920
• Publications: 16 publications found

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:41998): (CHKB-CPT1B readthrough (NMD candidate)) The genes CHKB and CPT1B are adjacent on chromosome 22 and read-through transcripts are expressed that include exons from both loci. The read-through transcripts are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to express proteins. [provided by RefSeq, Jun 2009]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 128729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
CHKB	NM_005198.5	c.333+10G>T		intron_variant	Intron 2 of 10	ENST00000406938.3	NP_005189.2
CHKB-CPT1B	NR_027928.2	n.551+10G>T		intron_variant	Intron 2 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHKB	ENST00000406938.3	c.333+10G>T		intron_variant	Intron 2 of 10	1	NM_005198.5	ENSP00000384400.3

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

GnomAD2 exomes AF: 0.657 AC: 124660 AN: 189754 AF XY: 0.652

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 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

African (AFR) AF: 0.575 AC: 18762 AN: 32638

American (AMR) AF: 0.746 AC: 29152 AN: 39056

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 14658 AN: 25364

East Asian (EAS) AF: 0.960 AC: 36331 AN: 37836

South Asian (SAS) AF: 0.697 AC: 56441 AN: 80932

European-Finnish (FIN) AF: 0.642 AC: 31743 AN: 49416

Middle Eastern (MID) AF: 0.502 AC: 2079 AN: 4140

European-Non Finnish (NFE) AF: 0.574 AC: 626711 AN: 1092264

Other (OTH) AF: 0.601 AC: 35285 AN: 58750

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

African (AFR) AF: 0.568 AC: 23560 AN: 41458

American (AMR) AF: 0.669 AC: 10223 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1989 AN: 3466

East Asian (EAS) AF: 0.970 AC: 4982 AN: 5134

South Asian (SAS) AF: 0.718 AC: 3459 AN: 4820

European-Finnish (FIN) AF: 0.657 AC: 6946 AN: 10568

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38790 AN: 67904

Other (OTH) AF: 0.588 AC: 1240 AN: 2110

Alfa AF: 0.551 Hom.: 7881

Bravo AF: 0.607

Asia WGS AF: 0.840 AC: 2920 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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. -

Dec 02, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Megaconial type congenital muscular dystrophy Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.2
DANN	Benign	0.69
PhyloP100		0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs86337; hg19: chr22-51020668;