Genetic Variant CHKB-DT:n.145C>T (chr22-50583170-C-T) – 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.145C>T 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 0.462 in 197,042 control chromosomes in the GnomAD database, including 22,669 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 16828 hom., cov: 34)

Exomes 𝑓: 0.50 ( 5841 hom. )

Consequence

CHKB-DT
ENST00000380711.3 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.29

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=-0.87).

BP6

Variant 22-50583170-C-T is Benign according to our data. Variant chr22-50583170-C-T is described in ClinVar as [Benign]. Clinvar id is 668084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
CHKB-DT	NR_021492.2 link	n.145C>T	non_coding_transcript_exon_variant	Exon 1 of 2
CHKB-DT	NR_110536.1 link	n.145C>T	non_coding_transcript_exon_variant	Exon 1 of 4
CHKB-CPT1B	NR_027928.2 link	n.-171G>A	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CHKB-DT	ENST00000380711.3 link	n.145C>T	non_coding_transcript_exon_variant	Exon 1 of 2	2
CHKB-DT	ENST00000648558.1 link	n.15C>T	non_coding_transcript_exon_variant	Exon 1 of 4
CHKB-DT	ENST00000656328.1 link	n.51C>T	non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

68655

AN:

151818

Hom.:

16828

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.681

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.489

Gnomad EAS

AF:

0.573

Gnomad SAS

AF:

0.559

Gnomad FIN

AF:

0.585

Gnomad MID

AF:

0.404

Gnomad NFE

AF:

0.520

Gnomad OTH

AF:

0.455

GnomAD4 exome

AF:

0.497

AC:

22407

AN:

45110

Hom.:

5841

Cov.:

AF XY:

0.496

AC XY:

11655

AN XY:

23482

show subpopulations

Gnomad4 AFR exome

AF:

0.269

Gnomad4 AMR exome

AF:

0.524

Gnomad4 ASJ exome

AF:

0.468

Gnomad4 EAS exome

AF:

0.563

Gnomad4 SAS exome

AF:

0.502

Gnomad4 FIN exome

AF:

0.528

Gnomad4 NFE exome

AF:

0.502

Gnomad4 OTH exome

AF:

0.469

GnomAD4 genome

AF:

0.452

AC:

68683

AN:

151932

Hom.:

16828

Cov.:

AF XY:

0.459

AC XY:

34067

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.245

Gnomad4 AMR

AF:

0.525

Gnomad4 ASJ

AF:

0.489

Gnomad4 EAS

AF:

0.572

Gnomad4 SAS

AF:

0.560

Gnomad4 FIN

AF:

0.585

Gnomad4 NFE

AF:

0.520

Gnomad4 OTH

AF:

0.459

Alfa

AF:

0.441

Hom.:

3270

Bravo

AF:

0.440

Asia WGS

AF:

0.581

AC:

2015

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 19, 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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.1

DANN

Benign

0.85

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