Variant chr22-50580482-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005198.5(CHKB):c.678-66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 1,609,144 control chromosomes in the GnomAD database, including 4,679 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.064 ( 477 hom., cov: 32)

Exomes 𝑓: 0.061 ( 4202 hom. )

Consequence

CHKB
NM_005198.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.612

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

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

BP6

Variant 22-50580482-C-T is Benign according to our data. Variant chr22-50580482-C-T is described in ClinVar as [Benign]. Clinvar id is 676260.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-50580482-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHKB	NM_005198.5 linkuse as main transcript	c.678-66G>A		intron_variant		ENST00000406938.3
CHKB-CPT1B	NR_027928.2 linkuse as main transcript	n.896-66G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHKB	ENST00000406938.3 linkuse as main transcript	c.678-66G>A		intron_variant		1	NM_005198.5	P1	Q9Y259-1

Frequencies

GnomAD3 genomes

AF:

0.0635

AC:

9664

AN:

152112

Hom.:

476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0496

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.0423

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0517

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0476

Gnomad OTH

AF:

0.0552

GnomAD4 exome

AF:

0.0613

AC:

89286

AN:

1456914

Hom.:

4202

Cov.:

AF XY:

0.0623

AC XY:

45181

AN XY:

725118

show subpopulations

Gnomad4 AFR exome

AF:

0.0477

Gnomad4 AMR exome

AF:

0.180

Gnomad4 ASJ exome

AF:

0.0457

Gnomad4 EAS exome

AF:

0.231

Gnomad4 SAS exome

AF:

0.111

Gnomad4 FIN exome

AF:

0.0540

Gnomad4 NFE exome

AF:

0.0475

Gnomad4 OTH exome

AF:

0.0668

GnomAD4 genome

AF:

0.0636

AC:

9680

AN:

152230

Hom.:

477

Cov.:

AF XY:

0.0660

AC XY:

4912

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0496

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.0423

Gnomad4 EAS

AF:

0.246

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.0517

Gnomad4 NFE

AF:

0.0476

Gnomad4 OTH

AF:

0.0575

Alfa

AF:

0.0548

Hom.:

147

Bravo

AF:

0.0683

Asia WGS

AF:

0.177

AC:

613

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.87

CADD

Benign

0.080

DANN

Benign

0.38

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