22-50579284-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005198.5(CHKB):c.1114-29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.077 in 1,609,802 control chromosomes in the GnomAD database, including 8,290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1169 hom., cov: 32)
  • Exomes 𝑓: 0.074 (7121 hom.)
• Consequence: CHKB NM_005198.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.33

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-CPT1B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 22-50579284-G-A is Benign according to our data. Variant chr22-50579284-G-A is described in ClinVar as [Benign]. Clinvar id is 1275585.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-50579284-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHKB	NM_005198.5	c.1114-29C>T		intron_variant		ENST00000406938.3
CHKB-CPT1B	NR_027928.2	n.1332-29C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHKB	ENST00000406938.3	c.1114-29C>T		intron_variant		1	NM_005198.5	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15309 AN: 151972 Hom.: 1166 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0712

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0525

Gnomad OTH AF: 0.0839

GnomAD3 exomes AF: 0.120 AC: 29102 AN: 242458 Hom.: 3011 AF XY: 0.115 AC XY: 15072 AN XY: 131604

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.201

Gnomad ASJ exome AF: 0.0521

Gnomad EAS exome AF: 0.413

Gnomad SAS exome AF: 0.142

Gnomad FIN exome AF: 0.0715

Gnomad NFE exome AF: 0.0527

Gnomad OTH exome AF: 0.0876

GnomAD4 exome AF: 0.0745 AC: 108567 AN: 1457712 Hom.: 7121 Cov.: 30 AF XY: 0.0759 AC XY: 55048 AN XY: 725172

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.0532

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.0687

Gnomad4 NFE exome AF: 0.0522

Gnomad4 OTH exome AF: 0.0864

GnomAD4 genome AF: 0.101 AC: 15343 AN: 152090 Hom.: 1169 Cov.: 32 AF XY: 0.105 AC XY: 7819 AN XY: 74342

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0513

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.0712

Gnomad4 NFE AF: 0.0525

Gnomad4 OTH AF: 0.0863

Alfa AF: 0.0693 Hom.: 108

Bravo AF: 0.108

Asia WGS AF: 0.252 AC: 877 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.7
Dann	Benign	0.74

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

Other links and lift over

dbSNP: rs762677; hg19: chr22-51017713; COSMIC: COSV56415516; COSMIC: COSV56415516;