rs5770917

Positions:

• chr22-50578924-T-C
• chr22-50578924-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NR_027928.2(CHKB-CPT1B):​n.1551+112A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 559,868 control chromosomes in the GnomAD database, including 2,222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (495 hom., cov: 33)
  • Exomes 𝑓: 0.071 (1727 hom.)
• Consequence: CHKB-CPT1B NR_027928.2 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.60

Genes affected

CHKB-CPT1B (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 22-50578924-T-C is Benign according to our data. Variant chr22-50578924-T-C is described in ClinVar as [Benign]. Clinvar id is 1231742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50578924-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHKB-CPT1B	NR_027928.2	n.1551+112A>G		intron_variant, non_coding_transcript_variant
CHKB	NM_005198.5			downstream_gene_variant		ENST00000406938.3	NP_005189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHKB	ENST00000406938.3			downstream_gene_variant		1	NM_005198.5	ENSP00000384400	P1

Frequencies

GnomAD3 genomes AF: 0.0639 AC: 9716 AN: 152158 Hom.: 494 Cov.: 33

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0476

Gnomad OTH AF: 0.0549

GnomAD4 exome AF: 0.0712 AC: 29005 AN: 407592 Hom.: 1727 Cov.: 0 AF XY: 0.0734 AC XY: 15890 AN XY: 216366

Gnomad4 AFR exome AF: 0.0502

Gnomad4 AMR exome AF: 0.151

Gnomad4 ASJ exome AF: 0.0446

Gnomad4 EAS exome AF: 0.227

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.0520

Gnomad4 NFE exome AF: 0.0457

Gnomad4 OTH exome AF: 0.0653

GnomAD4 genome AF: 0.0639 AC: 9732 AN: 152276 Hom.: 495 Cov.: 33 AF XY: 0.0663 AC XY: 4934 AN XY: 74460

Gnomad4 AFR AF: 0.0496

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0424

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0520

Gnomad4 NFE AF: 0.0476

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0513 Hom.: 420

Bravo AF: 0.0689

Asia WGS AF: 0.178 AC: 619 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs5770917; hg19: chr22-51017353;