rs180979987

chr22-50582333-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS1

The NM_005198.5(CHKB):c.249C>T(p.Phe83=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00307 in 1,574,022 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (7 hom.)
• Consequence: CHKB NM_005198.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 4.59

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 22-50582333-G-A is Benign according to our data. Variant chr22-50582333-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 342176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50582333-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00171 (260/152270) while in subpopulation NFE AF= 0.00338 (230/68000). AF 95% confidence interval is 0.00302. There are 1 homozygotes in gnomad4. There are 104 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHKB	NM_005198.5	c.249C>T	p.Phe83=	synonymous_variant	2/11	ENST00000406938.3
CHKB-CPT1B	NR_027928.2	n.467C>T		non_coding_transcript_exon_variant	2/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHKB	ENST00000406938.3	c.249C>T	p.Phe83=	synonymous_variant	2/11	1	NM_005198.5	P1

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 260 AN: 152152 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00338

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00187 AC: 338 AN: 180366 Hom.: 0 AF XY: 0.00176 AC XY: 172 AN XY: 97824

Gnomad AFR exome AF: 0.000189

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00126

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000528

Gnomad NFE exome AF: 0.00410

Gnomad OTH exome AF: 0.00146

GnomAD4 exome AF: 0.00321 AC: 4565 AN: 1421752 Hom.: 7 Cov.: 32 AF XY: 0.00310 AC XY: 2182 AN XY: 703948

Gnomad4 AFR exome AF: 0.000244

Gnomad4 AMR exome AF: 0.000128

Gnomad4 ASJ exome AF: 0.00122

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000123

Gnomad4 FIN exome AF: 0.000498

Gnomad4 NFE exome AF: 0.00402

Gnomad4 OTH exome AF: 0.00168

GnomAD4 genome AF: 0.00171 AC: 260 AN: 152270 Hom.: 1 Cov.: 33 AF XY: 0.00140 AC XY: 104 AN XY: 74462

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00338

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00267 Hom.: 0

Bravo AF: 0.00178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	CHKB: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 18, 2021	- -

Megaconial type congenital muscular dystrophy Benign:2

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 04, 2024	- -

CHKB-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 27, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Benign	14
Dann	Benign	0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs180979987; hg19: chr22-51020762;