chr22-50583150-A-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000380711.3(CHKB-DT):​n.125A>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 0.82 in 229,798 control chromosomes in the GnomAD database, including 78,290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (54183 hom., cov: 36)
  • Exomes 𝑓: 0.78 (24107 hom.)
• Consequence: CHKB-DT ENST00000380711.3 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 22-50583150-A-C is Benign according to our data. Variant chr22-50583150-A-C is described in ClinVar as Benign. ClinVar VariationId is 668085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

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>C		non_coding_transcript_exon	Exon 1 of 2
	CHKB-DT	NR_110536.1		n.125A>C		non_coding_transcript_exon	Exon 1 of 4
	CHKB-CPT1B	NR_027928.2		n.-151T>G		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>C		non_coding_transcript_exon	Exon 1 of 2
	CHKB-DT	ENST00000656328.1		n.31A>C		non_coding_transcript_exon	Exon 1 of 2
	CHKB-DT	ENST00000803313.1		n.27A>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127488 AN: 152016 Hom.: 54117 Cov.: 36

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.790

GnomAD4 exome AF: 0.784 AC: 60875 AN: 77668 Hom.: 24107 Cov.: 0 AF XY: 0.787 AC XY: 31729 AN XY: 40296

African (AFR) AF: 0.950 AC: 2036 AN: 2144

American (AMR) AF: 0.830 AC: 1407 AN: 1696

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 1891 AN: 2724

East Asian (EAS) AF: 0.964 AC: 4882 AN: 5062

South Asian (SAS) AF: 0.851 AC: 5928 AN: 6970

European-Finnish (FIN) AF: 0.824 AC: 3913 AN: 4750

Middle Eastern (MID) AF: 0.723 AC: 276 AN: 382

European-Non Finnish (NFE) AF: 0.750 AC: 36693 AN: 48948

Other (OTH) AF: 0.771 AC: 3849 AN: 4992

GnomAD4 genome AF: 0.839 AC: 127610 AN: 152130 Hom.: 54183 Cov.: 36 AF XY: 0.845 AC XY: 62840 AN XY: 74368

African (AFR) AF: 0.959 AC: 39851 AN: 41574

American (AMR) AF: 0.820 AC: 12541 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2473 AN: 3464

East Asian (EAS) AF: 0.987 AC: 5087 AN: 5154

South Asian (SAS) AF: 0.880 AC: 4253 AN: 4832

European-Finnish (FIN) AF: 0.843 AC: 8923 AN: 10588

Middle Eastern (MID) AF: 0.733 AC: 214 AN: 292

European-Non Finnish (NFE) AF: 0.762 AC: 51768 AN: 67908

Other (OTH) AF: 0.793 AC: 1677 AN: 2114

Alfa AF: 0.806 Hom.: 6205

Bravo AF: 0.843

Asia WGS AF: 0.942 AC: 3274 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.18
PhyloP100		-2.9
PromoterAI		-0.22	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;