22-50579055-G-T

Variant names:

• chr22-50579055-G-T
• rs112742765
• NM_005198.5:c.*126C>A

Variant summary

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

The NM_005198.5(CHKB):​c.*126C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000134 in 744,524 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: 32)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: CHKB NM_005198.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 0 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=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005198.5. 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	NM_005198.5	MANE Select	c.*126C>A		3_prime_UTR	Exon 11 of 11	NP_005189.2
	CHKB-CPT1B	NR_027928.2		n.1532C>A		non_coding_transcript_exon	Exon 11 of 30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHKB	ENST00000406938.3	TSL:1 MANE Select	c.*126C>A		3_prime_UTR	Exon 11 of 11	ENSP00000384400.3	Q9Y259-1
	CHKB-CPT1B	ENST00000453634.5	TSL:5	n.*126C>A		non_coding_transcript_exon	Exon 3 of 23	ENSP00000457031.1	H3BT56
	CHKB	ENST00000481673.5	TSL:1	n.1764C>A		non_coding_transcript_exon	Exon 10 of 10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000134 AC: 1 AN: 744524 Hom.: 0 Cov.: 10 AF XY: 0.00000257 AC XY: 1 AN XY: 389448

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18944

American (AMR) AF: 0.00 AC: 0 AN: 34656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20878

East Asian (EAS) AF: 0.00 AC: 0 AN: 32752

South Asian (SAS) AF: 0.00 AC: 0 AN: 65650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3448

European-Non Finnish (NFE) AF: 0.00000206 AC: 1 AN: 484428

Other (OTH) AF: 0.00 AC: 0 AN: 36436

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.69
PhyloP100		-0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs112742765; hg19: chr22-51017484;