rs80067609

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000406938.3(CHKB):c.216C>T(p.Tyr72=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 1,609,032 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 96 hom., cov: 34)

Exomes 𝑓: 0.0018 ( 57 hom. )

Consequence

CHKB
ENST00000406938.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.749

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:):

CHKB-CPT1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 22-50582566-G-A is Benign according to our data. Variant chr22-50582566-G-A is described in ClinVar as [Benign]. Clinvar id is 128728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.749 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHKB	NM_005198.5 linkuse as main transcript	c.216C>T	p.Tyr72=	synonymous_variant	1/11	ENST00000406938.3	NP_005189.2
CHKB-CPT1B	NR_027928.2 linkuse as main transcript	n.434C>T		non_coding_transcript_exon_variant	1/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHKB	ENST00000406938.3 linkuse as main transcript	c.216C>T	p.Tyr72=	synonymous_variant	1/11	1	NM_005198.5	ENSP00000384400	P1	Q9Y259-1

Frequencies

GnomAD3 genomes

AF:

0.0166

AC:

2523

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0571

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00416

AC:

965

AN:

232040

Hom.:

AF XY:

0.00319

AC XY:

410

AN XY:

128356

show subpopulations

Gnomad AFR exome

AF:

0.0562

Gnomad AMR exome

AF:

0.00354

Gnomad ASJ exome

AF:

0.000105

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000334

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000503

Gnomad OTH exome

AF:

0.00263

GnomAD4 exome

AF:

0.00184

AC:

2687

AN:

1456746

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

1173

AN XY:

724566

show subpopulations

Gnomad4 AFR exome

AF:

0.0552

Gnomad4 AMR exome

AF:

0.00411

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000582

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000361

Gnomad4 OTH exome

AF:

0.00378

GnomAD4 genome

AF:

0.0166

AC:

2534

AN:

152286

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

1226

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0572

Gnomad4 AMR

AF:

0.00654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00100

Hom.:

Bravo

AF:

0.0192

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000714

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 16, 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. -
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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 07, 2017	- -

Megaconial type congenital muscular dystrophy

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.94

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

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