22-50583150-A-G

Variant names:

• chr22-50583150-A-G
• rs131757
• ENST00000380711.3:n.125A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000380711.3(CHKB-DT):​n.125A>G 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. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 36)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHKB-DT ENST00000380711.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.94
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

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.125A>G		non_coding_transcript_exon	Exon 1 of 2
	CHKB-DT	NR_110536.1		n.125A>G		non_coding_transcript_exon	Exon 1 of 4
	CHKB-CPT1B	NR_027928.2		n.-151T>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHKB-DT	ENST00000380711.3	TSL:2	n.125A>G		non_coding_transcript_exon	Exon 1 of 2
	CHKB-DT	ENST00000656328.1		n.31A>G		non_coding_transcript_exon	Exon 1 of 2
	CHKB-DT	ENST00000803313.1		n.27A>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 77958 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 40432

African (AFR) AF: 0.00 AC: 0 AN: 2144

American (AMR) AF: 0.00 AC: 0 AN: 1702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2736

East Asian (EAS) AF: 0.00 AC: 0 AN: 5064

South Asian (SAS) AF: 0.00 AC: 0 AN: 6986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 386

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 49150

Other (OTH) AF: 0.00 AC: 0 AN: 5018

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.4
DANN	Benign	0.48
PhyloP100		-2.9
PromoterAI		-0.45	Neutral

Splicing

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

Other links and lift over

dbSNP: rs131757; hg19: chr22-51021579;