22-50583170-C-T

Variant names:

• chr22-50583170-C-T
• rs131756
• ENST00000380711.3:n.145C>T

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.145C>T 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 0.462 in 197,042 control chromosomes in the GnomAD database, including 22,669 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (16828 hom., cov: 34)
  • Exomes 𝑓: 0.50 (5841 hom.)
• Consequence: CHKB-DT ENST00000380711.3 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.29
• Publications: 13 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=-0.87).
• BP6: Variant 22-50583170-C-T is Benign according to our data. Variant chr22-50583170-C-T is described in ClinVar as Benign. ClinVar VariationId is 668084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 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.145C>T		non_coding_transcript_exon	Exon 1 of 2
	CHKB-DT	NR_110536.1		n.145C>T		non_coding_transcript_exon	Exon 1 of 4
	CHKB-CPT1B	NR_027928.2		n.-171G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHKB-DT	ENST00000380711.3	TSL:2	n.145C>T		non_coding_transcript_exon	Exon 1 of 2
	CHKB-DT	ENST00000648558.1		n.15C>T		non_coding_transcript_exon	Exon 1 of 4
	CHKB-DT	ENST00000656328.1		n.51C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68655 AN: 151818 Hom.: 16828 Cov.: 34

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.497 AC: 22407 AN: 45110 Hom.: 5841 Cov.: 0 AF XY: 0.496 AC XY: 11655 AN XY: 23482

African (AFR) AF: 0.269 AC: 346 AN: 1284

American (AMR) AF: 0.524 AC: 496 AN: 946

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 720 AN: 1538

East Asian (EAS) AF: 0.563 AC: 1399 AN: 2486

South Asian (SAS) AF: 0.502 AC: 2328 AN: 4640

European-Finnish (FIN) AF: 0.528 AC: 1321 AN: 2504

Middle Eastern (MID) AF: 0.449 AC: 97 AN: 216

European-Non Finnish (NFE) AF: 0.502 AC: 14330 AN: 28574

Other (OTH) AF: 0.469 AC: 1370 AN: 2922

GnomAD4 genome AF: 0.452 AC: 68683 AN: 151932 Hom.: 16828 Cov.: 34 AF XY: 0.459 AC XY: 34067 AN XY: 74266

African (AFR) AF: 0.245 AC: 10163 AN: 41468

American (AMR) AF: 0.525 AC: 8023 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1694 AN: 3466

East Asian (EAS) AF: 0.572 AC: 2936 AN: 5132

South Asian (SAS) AF: 0.560 AC: 2697 AN: 4820

European-Finnish (FIN) AF: 0.585 AC: 6190 AN: 10584

Middle Eastern (MID) AF: 0.403 AC: 117 AN: 290

European-Non Finnish (NFE) AF: 0.520 AC: 35272 AN: 67864

Other (OTH) AF: 0.459 AC: 971 AN: 2114

Alfa AF: 0.438 Hom.: 3673

Bravo AF: 0.440

Asia WGS AF: 0.581 AC: 2015 AN: 3474

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	-0.87
CADD	Benign	3.1
DANN	Benign	0.85
PhyloP100		-1.3
PromoterAI		0.14	Neutral

Splicing

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

Other links and lift over

dbSNP: rs131756; hg19: chr22-51021599;