Variant 22-50579085-C-G 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.*96G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 1,231,266 control chromosomes in the GnomAD database, including 1,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 195 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1452 hom. )

Consequence

CHKB
NM_005198.5 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.182

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 22-50579085-C-G is Benign according to our data. Variant chr22-50579085-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 342164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 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.*96G>C		3_prime_UTR_variant	11/11	ENST00000406938.3
CHKB-CPT1B	NR_027928.2 linkuse as main transcript	n.1502G>C		non_coding_transcript_exon_variant	11/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHKB	ENST00000406938.3 linkuse as main transcript	c.*96G>C		3_prime_UTR_variant	11/11	1	NM_005198.5	P1	Q9Y259-1

Frequencies

GnomAD3 genomes

AF:

0.0355

AC:

5401

AN:

152182

Hom.:

197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.0396

Gnomad AMR

AF:

0.0755

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.0586

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0255

Gnomad OTH

AF:

0.0388

GnomAD4 exome

AF:

0.0369

AC:

39767

AN:

1078966

Hom.:

1452

Cov.:

AF XY:

0.0400

AC XY:

21844

AN XY:

546558

show subpopulations

Gnomad4 AFR exome

AF:

0.0111

Gnomad4 AMR exome

AF:

0.0803

Gnomad4 ASJ exome

AF:

0.0335

Gnomad4 EAS exome

AF:

0.112

Gnomad4 SAS exome

AF:

0.128

Gnomad4 FIN exome

AF:

0.0520

Gnomad4 NFE exome

AF:

0.0229

Gnomad4 OTH exome

AF:

0.0388

GnomAD4 genome

AF:

0.0355

AC:

5408

AN:

152300

Hom.:

195

Cov.:

AF XY:

0.0407

AC XY:

3034

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.0754

Gnomad4 ASJ

AF:

0.0308

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.135

Gnomad4 FIN

AF:

0.0586

Gnomad4 NFE

AF:

0.0255

Gnomad4 OTH

AF:

0.0393

Alfa

AF:

0.0284

Hom.:

Bravo

AF:

0.0325

Asia WGS

AF:

0.130

AC:

449

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Megaconial type congenital muscular dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.4

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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