22-50580482-C-T

Variant names:

• chr22-50580482-C-T
• rs2269382
• NM_005198.5:c.678-66G>A

Variant summary

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

The NM_005198.5(CHKB):​c.678-66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 1,609,144 control chromosomes in the GnomAD database, including 4,679 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (477 hom., cov: 32)
  • Exomes 𝑓: 0.061 (4202 hom.)
• Consequence: CHKB NM_005198.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.612
• Publications: 10 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 22-50580482-C-T is Benign according to our data. Variant chr22-50580482-C-T is described in ClinVar as Benign. ClinVar VariationId is 676260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHKB	NM_005198.5	MANE Select	c.678-66G>A		intron	N/A	NP_005189.2
	CHKB-CPT1B	NR_027928.2		n.896-66G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHKB	ENST00000406938.3	TSL:1 MANE Select	c.678-66G>A		intron	N/A	ENSP00000384400.3
	CHKB	ENST00000481673.5	TSL:1	n.1128-66G>A		intron	N/A
	CHKB	ENST00000939160.1		c.759-66G>A		intron	N/A	ENSP00000609219.1

Frequencies

GnomAD3 genomes AF: 0.0635 AC: 9664 AN: 152112 Hom.: 476 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0517

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0476

Gnomad OTH AF: 0.0552

GnomAD4 exome AF: 0.0613 AC: 89286 AN: 1456914 Hom.: 4202 Cov.: 31 AF XY: 0.0623 AC XY: 45181 AN XY: 725118

African (AFR) AF: 0.0477 AC: 1592 AN: 33368

American (AMR) AF: 0.180 AC: 8062 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0457 AC: 1192 AN: 26104

East Asian (EAS) AF: 0.231 AC: 9174 AN: 39682

South Asian (SAS) AF: 0.111 AC: 9559 AN: 86146

European-Finnish (FIN) AF: 0.0540 AC: 2881 AN: 53322

Middle Eastern (MID) AF: 0.0373 AC: 207 AN: 5548

European-Non Finnish (NFE) AF: 0.0475 AC: 52598 AN: 1107820

Other (OTH) AF: 0.0668 AC: 4021 AN: 60208

GnomAD4 genome AF: 0.0636 AC: 9680 AN: 152230 Hom.: 477 Cov.: 32 AF XY: 0.0660 AC XY: 4912 AN XY: 74436

African (AFR) AF: 0.0496 AC: 2062 AN: 41552

American (AMR) AF: 0.109 AC: 1664 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0423 AC: 147 AN: 3472

East Asian (EAS) AF: 0.246 AC: 1272 AN: 5170

South Asian (SAS) AF: 0.126 AC: 609 AN: 4820

European-Finnish (FIN) AF: 0.0517 AC: 548 AN: 10606

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0476 AC: 3238 AN: 67996

Other (OTH) AF: 0.0575 AC: 121 AN: 2106

Alfa AF: 0.0541 Hom.: 161

Bravo AF: 0.0683

Asia WGS AF: 0.177 AC: 613 AN: 3478

ClinVar

ClinVar submissions as Germline

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	0.080
DANN	Benign	0.38
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2269382; hg19: chr22-51018911; COSMIC: COSV56417669; COSMIC: COSV56417669;