rs199703765

chr22-50582768-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS1

The NM_005198.5(CHKB):c.14C>T(p.Ala5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000422 in 1,577,516 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00081 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00038 (2 hom.)
• Consequence: CHKB NM_005198.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0100

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 -12 ACMG points.

• BP6: Variant 22-50582768-G-A is Benign according to our data. Variant chr22-50582768-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 383214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000814 (124/152310) while in subpopulation AMR AF= 0.00255 (39/15310). AF 95% confidence interval is 0.00192. There are 0 homozygotes in gnomad4. There are 59 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHKB	NM_005198.5	c.14C>T	p.Ala5Val	missense_variant	1/11	ENST00000406938.3
CHKB-CPT1B	NR_027928.2	n.232C>T		non_coding_transcript_exon_variant	1/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHKB	ENST00000406938.3	c.14C>T	p.Ala5Val	missense_variant	1/11	1	NM_005198.5	P1

Frequencies

GnomAD3 genomes AF: 0.000815 AC: 124 AN: 152192 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000608 AC: 105 AN: 172824 Hom.: 0 AF XY: 0.000677 AC XY: 65 AN XY: 95980

Gnomad AFR exome AF: 0.00195

Gnomad AMR exome AF: 0.00118

Gnomad ASJ exome AF: 0.00140

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000642

Gnomad NFE exome AF: 0.000535

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000380 AC: 541 AN: 1425206 Hom.: 2 Cov.: 32 AF XY: 0.000415 AC XY: 293 AN XY: 706510

Gnomad4 AFR exome AF: 0.000963

Gnomad4 AMR exome AF: 0.00136

Gnomad4 ASJ exome AF: 0.00138

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000417

Gnomad4 NFE exome AF: 0.000301

Gnomad4 OTH exome AF: 0.00131

GnomAD4 genome AF: 0.000814 AC: 124 AN: 152310 Hom.: 0 Cov.: 34 AF XY: 0.000792 AC XY: 59 AN XY: 74488

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000471

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000457 Hom.: 0

Bravo AF: 0.000895

ExAC AF: 0.000460 AC: 52

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2016

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:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.092	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.0060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.032
Sift	Benign	0.054	T
Sift4G	Benign	0.17	T
Polyphen		0.0060	B
Vest4		0.16
MutPred		0.33		Gain of sheet (P = 0.0028);
MVP		0.45
ClinPred		0.028	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.040
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.27		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs199703765; hg19: chr22-51021197;