chr22-50582239-C-G

Variant names:

• chr22-50582239-C-G
• rs86337
• ENST00000481673.5:n.407G>C

Variant summary

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

The ENST00000481673.5(CHKB):​n.407G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000774 in 1,421,240 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000077 (0 hom.)
• Consequence: CHKB ENST00000481673.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.920
• Publications: 16 publications found

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: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=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHKB	NM_005198.5	c.333+10G>C		intron_variant	Intron 2 of 10	ENST00000406938.3	NP_005189.2
CHKB-CPT1B	NR_027928.2	n.551+10G>C		intron_variant	Intron 2 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHKB	ENST00000406938.3	c.333+10G>C		intron_variant	Intron 2 of 10	1	NM_005198.5	ENSP00000384400.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000774 AC: 11 AN: 1421240 Hom.: 0 Cov.: 32 AF XY: 0.00000853 AC XY: 6 AN XY: 703732

African (AFR) AF: 0.00 AC: 0 AN: 32652

American (AMR) AF: 0.00 AC: 0 AN: 39066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25376

East Asian (EAS) AF: 0.00 AC: 0 AN: 37838

South Asian (SAS) AF: 0.00 AC: 0 AN: 80958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4140

European-Non Finnish (NFE) AF: 0.00000915 AC: 10 AN: 1092934

Other (OTH) AF: 0.0000170 AC: 1 AN: 58776

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 7881

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.4
DANN	Benign	0.53
PhyloP100		0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs86337; hg19: chr22-51020668;