Genetic Variant CHKB-DT:n.125A>C (chr22-50583150-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The ENST00000380711.3(CHKB-DT):n.125A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 229,798 control chromosomes in the GnomAD database, including 78,290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 54183 hom., cov: 36)

Exomes 𝑓: 0.78 ( 24107 hom. )

Consequence

CHKB-DT
ENST00000380711.3 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.94

Variant links:

Genes affected

CHKB-DT (HGNC:40146): (CHKB divergent transcript)

CHKB-DT links:

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 22-50583150-A-C is Benign according to our data. Variant chr22-50583150-A-C is described in ClinVar as [Benign]. Clinvar id is 668085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
CHKB-DT	NR_021492.2 link	n.125A>C	non_coding_transcript_exon_variant	Exon 1 of 2
CHKB-DT	NR_110536.1 link	n.125A>C	non_coding_transcript_exon_variant	Exon 1 of 4
CHKB-CPT1B	NR_027928.2 link	n.-151T>G	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CHKB-DT	ENST00000380711.3 link	n.125A>C	non_coding_transcript_exon_variant	Exon 1 of 2	2
CHKB-DT	ENST00000656328.1 link	n.31A>C	non_coding_transcript_exon_variant	Exon 1 of 2
CHKB	ENST00000463053.1 link	n.307-793T>G	intron_variant	Intron 1 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.839

AC:

127488

AN:

152016

Hom.:

54117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.958

Gnomad AMI

AF:

0.904

Gnomad AMR

AF:

0.820

Gnomad ASJ

AF:

0.714

Gnomad EAS

AF:

0.987

Gnomad SAS

AF:

0.880

Gnomad FIN

AF:

0.843

Gnomad MID

AF:

0.732

Gnomad NFE

AF:

0.762

Gnomad OTH

AF:

0.790

GnomAD4 exome

AF:

0.784

AC:

60875

AN:

77668

Hom.:

24107

Cov.:

AF XY:

0.787

AC XY:

31729

AN XY:

40296

show subpopulations

Gnomad4 AFR exome

AF:

0.950

Gnomad4 AMR exome

AF:

0.830

Gnomad4 ASJ exome

AF:

0.694

Gnomad4 EAS exome

AF:

0.964

Gnomad4 SAS exome

AF:

0.851

Gnomad4 FIN exome

AF:

0.824

Gnomad4 NFE exome

AF:

0.750

Gnomad4 OTH exome

AF:

0.771

GnomAD4 genome

AF:

0.839

AC:

127610

AN:

152130

Hom.:

54183

Cov.:

AF XY:

0.845

AC XY:

62840

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.959

Gnomad4 AMR

AF:

0.820

Gnomad4 ASJ

AF:

0.714

Gnomad4 EAS

AF:

0.987

Gnomad4 SAS

AF:

0.880

Gnomad4 FIN

AF:

0.843

Gnomad4 NFE

AF:

0.762

Gnomad4 OTH

AF:

0.793

Alfa

AF:

0.806

Hom.:

6205

Bravo

AF:

0.843

Asia WGS

AF:

0.942

AC:

3274

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-0.91

CADD

Benign

3.0

DANN

Benign

0.18

Splicing

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