chr22-50583170-C-T

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

2

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 (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-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]

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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 HGVSp Effect Exon rank MANE Protein UniProt
CHKB-DTNR_021492.2 linkn.145C>T non_coding_transcript_exon_variant Exon 1 of 2
CHKB-DTNR_110536.1 linkn.145C>T non_coding_transcript_exon_variant Exon 1 of 4
CHKB-CPT1BNR_027928.2 linkn.-171G>A upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHKB-DTENST00000380711.3 linkn.145C>T non_coding_transcript_exon_variant Exon 1 of 2 2
CHKB-DTENST00000648558.1 linkn.15C>T non_coding_transcript_exon_variant Exon 1 of 4
CHKB-DTENST00000656328.1 linkn.51C>T non_coding_transcript_exon_variant Exon 1 of 2

Frequencies

GnomAD3 genomes
AF:
0.452
AC:
68655
AN:
151818
Hom.:
16828
Cov.:
34
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.:
0
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.:
34
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.

Other links and lift over

dbSNP: rs131756; hg19: chr22-51021599; API