Variant rs2269381 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.448-87C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0617 in 1,597,734 control chromosomes in the GnomAD database, including 4,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 482 hom., cov: 32)

Exomes 𝑓: 0.061 ( 4200 hom. )

Consequence

CHKB
NM_005198.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.58

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 22-50581640-G-C is Benign according to our data. Variant chr22-50581640-G-C is described in ClinVar as [Benign]. Clinvar id is 676259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 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.448-87C>G		intron_variant		ENST00000406938.3	NP_005189.2
CHKB-CPT1B	NR_027928.2 linkuse as main transcript	n.666-87C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHKB	ENST00000406938.3 linkuse as main transcript	c.448-87C>G		intron_variant		1	NM_005198.5	ENSP00000384400	P1	Q9Y259-1

Frequencies

GnomAD3 genomes

AF:

0.0637

AC:

9693

AN:

152076

Hom.:

481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0502

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.0423

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0513

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0477

Gnomad OTH

AF:

0.0559

GnomAD4 exome

AF:

0.0615

AC:

88875

AN:

1445540

Hom.:

4200

Cov.:

AF XY:

0.0625

AC XY:

45016

AN XY:

720056

show subpopulations

Gnomad4 AFR exome

AF:

0.0483

Gnomad4 AMR exome

AF:

0.180

Gnomad4 ASJ exome

AF:

0.0457

Gnomad4 EAS exome

AF:

0.232

Gnomad4 SAS exome

AF:

0.111

Gnomad4 FIN exome

AF:

0.0538

Gnomad4 NFE exome

AF:

0.0476

Gnomad4 OTH exome

AF:

0.0673

GnomAD4 genome

AF:

0.0638

AC:

9709

AN:

152194

Hom.:

482

Cov.:

AF XY:

0.0662

AC XY:

4926

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0502

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.0423

Gnomad4 EAS

AF:

0.248

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.0513

Gnomad4 NFE

AF:

0.0477

Gnomad4 OTH

AF:

0.0581

Alfa

AF:

0.0540

Hom.:

Bravo

AF:

0.0686

Asia WGS

AF:

0.179

AC:

621

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 16, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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