22-50583192-CCGGCGGGG-CCGGCGGGGCGGCGGGGCGGCGGGGCGGCGGGG

Variant names:

• chr22-50583192-C-CCGGCGGGGCGGCGGGGCGGCGGGG
• rs538199922
• ENST00000380711.3:n.189_190insGGCGGCGGGGCGGCGGGGCGGCGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000380711.3(CHKB-DT):​n.189_190insGGCGGCGGGGCGGCGGGGCGGCGG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHKB-DT ENST00000380711.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000380711.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHKB-DT	NR_021492.2		n.189_190insGGCGGCGGGGCGGCGGGGCGGCGG		non_coding_transcript_exon	Exon 1 of 2
	CHKB-DT	NR_110536.1		n.189_190insGGCGGCGGGGCGGCGGGGCGGCGG		non_coding_transcript_exon	Exon 1 of 4
	CHKB-CPT1B	NR_027928.2		n.-194_-193insCCCCGCCGCCCCGCCGCCCCGCCG		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHKB-DT	ENST00000380711.3	TSL:2	n.189_190insGGCGGCGGGGCGGCGGGGCGGCGG		non_coding_transcript_exon	Exon 1 of 2
	CHKB-DT	ENST00000648558.1		n.59_60insGGCGGCGGGGCGGCGGGGCGGCGG		non_coding_transcript_exon	Exon 1 of 4
	CHKB-DT	ENST00000656328.1		n.95_96insGGCGGCGGGGCGGCGGGGCGGCGG		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs538199922; hg19: chr22-51021621;