rs199703765

Positions:

chr22-50582768-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0100

Variant links:

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 links:

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]

CHKB-CPT1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 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.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHKB	NM_005198.5 link	c.14C>T	p.Ala5Val	missense_variant	1/11	ENST00000406938.3	NP_005189.2	Q9Y259-1A0A024R4X4
CHKB-CPT1B	NR_027928.2 link	n.232C>T		non_coding_transcript_exon_variant	1/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHKB	ENST00000406938.3 link	c.14C>T	p.Ala5Val	missense_variant	1/11	1	NM_005198.5	ENSP00000384400.3		Q9Y259-1

Frequencies

GnomAD3 genomes

AF:

0.000815

AC:

124

AN:

152192

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.000677

AC XY:

AN XY:

95980

show subpopulations

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.:

Cov.:

AF XY:

0.000415

AC XY:

293

AN XY:

706510

show subpopulations

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.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74488

show subpopulations

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.:

Bravo

AF:

0.000895

ExAC

AF:

0.000460

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Megaconial type congenital muscular dystrophy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.092

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.46

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.0060

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.34

REVEL

Benign

0.032

Sift

Benign

0.054

Sift4G

Benign

0.17

Polyphen

0.0060

Vest4

0.16

MutPred

0.33

Gain of sheet (P = 0.0028);

MVP

0.45

ClinPred

0.028

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over