Variant 22-50579284-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005198.5(CHKB):c.1114-29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.077 in 1,609,802 control chromosomes in the GnomAD database, including 8,290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1169 hom., cov: 32)

Exomes 𝑓: 0.074 ( 7121 hom. )

Consequence

CHKB
NM_005198.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.33

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:

CHKB (HGNC:):

CHKB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 22-50579284-G-A is Benign according to our data. Variant chr22-50579284-G-A is described in ClinVar as [Benign]. Clinvar id is 1275585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50579284-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 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.1114-29C>T		intron_variant		ENST00000406938.3	NP_005189.2	Q9Y259-1A0A024R4X4
CHKB-CPT1B	NR_027928.2 linkuse as main transcript	n.1332-29C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHKB	ENST00000406938.3 linkuse as main transcript	c.1114-29C>T		intron_variant		1	NM_005198.5	ENSP00000384400.3		Q9Y259-1
CHKB-CPT1B	ENST00000453634.5 linkuse as main transcript	n.109-29C>T		intron_variant		5		ENSP00000457031.1		H3BT56

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15309

AN:

151972

Hom.:

1166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.0513

Gnomad EAS

AF:

0.387

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.0712

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0525

Gnomad OTH

AF:

0.0839

GnomAD3 exomes

AF:

0.120

AC:

29102

AN:

242458

Hom.:

3011

AF XY:

0.115

AC XY:

15072

AN XY:

131604

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.201

Gnomad ASJ exome

AF:

0.0521

Gnomad EAS exome

AF:

0.413

Gnomad SAS exome

AF:

0.142

Gnomad FIN exome

AF:

0.0715

Gnomad NFE exome

AF:

0.0527

Gnomad OTH exome

AF:

0.0876

GnomAD4 exome

AF:

0.0745

AC:

108567

AN:

1457712

Hom.:

7121

Cov.:

AF XY:

0.0759

AC XY:

55048

AN XY:

725172

show subpopulations

Gnomad4 AFR exome

AF:

0.146

Gnomad4 AMR exome

AF:

0.191

Gnomad4 ASJ exome

AF:

0.0532

Gnomad4 EAS exome

AF:

0.375

Gnomad4 SAS exome

AF:

0.139

Gnomad4 FIN exome

AF:

0.0687

Gnomad4 NFE exome

AF:

0.0522

Gnomad4 OTH exome

AF:

0.0864

GnomAD4 genome

AF:

0.101

AC:

15343

AN:

152090

Hom.:

1169

Cov.:

AF XY:

0.105

AC XY:

7819

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.143

Gnomad4 AMR

AF:

0.128

Gnomad4 ASJ

AF:

0.0513

Gnomad4 EAS

AF:

0.388

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.0712

Gnomad4 NFE

AF:

0.0525

Gnomad4 OTH

AF:

0.0863

Alfa

AF:

0.0693

Hom.:

108

Bravo

AF:

0.108

Asia WGS

AF:

0.252

AC:

877

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.7

DANN

Benign

0.74

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

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