rs2269381

chr22-50581640-G-C

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.448-87C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0617 in 1,597,734 control chromosomes in the GnomAD database, including 4,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.064 (482 hom., cov: 32)
  • Exomes 𝑓: 0.061 (4200 hom.)
• Consequence: CHKB NM_005198.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.58

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=-0.77).
• BP6: Variant 22-50581640-G-C is Benign according to our data. Variant chr22-50581640-G-C is described in ClinVar as [Benign]. Clinvar id is 676259.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHKB	NM_005198.5	c.448-87C>G		intron_variant		ENST00000406938.3
CHKB-CPT1B	NR_027928.2	n.666-87C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHKB	ENST00000406938.3	c.448-87C>G		intron_variant		1	NM_005198.5	P1

Frequencies

GnomAD3 genomes AF: 0.0637 AC: 9693 AN: 152076 Hom.: 481 Cov.: 32

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0513

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0477

Gnomad OTH AF: 0.0559

GnomAD4 exome AF: 0.0615 AC: 88875 AN: 1445540 Hom.: 4200 Cov.: 28 AF XY: 0.0625 AC XY: 45016 AN XY: 720056

Gnomad4 AFR exome AF: 0.0483

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.0457

Gnomad4 EAS exome AF: 0.232

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.0538

Gnomad4 NFE exome AF: 0.0476

Gnomad4 OTH exome AF: 0.0673

GnomAD4 genome AF: 0.0638 AC: 9709 AN: 152194 Hom.: 482 Cov.: 32 AF XY: 0.0662 AC XY: 4926 AN XY: 74394

Gnomad4 AFR AF: 0.0502

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0423

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.0513

Gnomad4 NFE AF: 0.0477

Gnomad4 OTH AF: 0.0581

Alfa AF: 0.0540 Hom.: 47

Bravo AF: 0.0686

Asia WGS AF: 0.179 AC: 621 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 16, 2018

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	-0.77
Cadd	Benign	15
Dann	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2269381; hg19: chr22-51020069; COSMIC: COSV56414886; COSMIC: COSV56414886;