rs2269381

Variant names:

• chr22-50581640-G-C
• rs2269381
• NM_005198.5:c.448-87C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-50581640-G-C
• chr22-50581640-G-T

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.448-87C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0617 in 1,597,734 control chromosomes in the GnomAD database, including 4,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (482 hom., cov: 32)
  • Exomes 𝑓: 0.061 (4200 hom.)
• Consequence: CHKB NM_005198.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.58
• Publications: 5 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=-0.77).
• BP6: Variant 22-50581640-G-C is Benign according to our data. Variant chr22-50581640-G-C is described in ClinVar as Benign. ClinVar VariationId is 676259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHKB	NM_005198.5	MANE Select	c.448-87C>G		intron	N/A	NP_005189.2
	CHKB-CPT1B	NR_027928.2		n.666-87C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHKB	ENST00000406938.3	TSL:1 MANE Select	c.448-87C>G		intron	N/A	ENSP00000384400.3	Q9Y259-1
	CHKB	ENST00000481673.5	TSL:1	n.898-87C>G		intron	N/A
	CHKB	ENST00000939160.1		c.515-73C>G		intron	N/A	ENSP00000609219.1

Frequencies

GnomAD3 genomes AF: 0.0637 AC: 9693 AN: 152076 Hom.: 481 Cov.: 32

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0513

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0477

Gnomad OTH AF: 0.0559

GnomAD4 exome AF: 0.0615 AC: 88875 AN: 1445540 Hom.: 4200 Cov.: 28 AF XY: 0.0625 AC XY: 45016 AN XY: 720056

African (AFR) AF: 0.0483 AC: 1600 AN: 33132

American (AMR) AF: 0.180 AC: 8018 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.0457 AC: 1190 AN: 26042

East Asian (EAS) AF: 0.232 AC: 9201 AN: 39618

South Asian (SAS) AF: 0.111 AC: 9532 AN: 85880

European-Finnish (FIN) AF: 0.0538 AC: 2849 AN: 52926

Middle Eastern (MID) AF: 0.0370 AC: 211 AN: 5698

European-Non Finnish (NFE) AF: 0.0476 AC: 52248 AN: 1097888

Other (OTH) AF: 0.0673 AC: 4026 AN: 59838

GnomAD4 genome AF: 0.0638 AC: 9709 AN: 152194 Hom.: 482 Cov.: 32 AF XY: 0.0662 AC XY: 4926 AN XY: 74394

African (AFR) AF: 0.0502 AC: 2086 AN: 41518

American (AMR) AF: 0.108 AC: 1659 AN: 15296

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

East Asian (EAS) AF: 0.248 AC: 1282 AN: 5166

South Asian (SAS) AF: 0.126 AC: 608 AN: 4816

European-Finnish (FIN) AF: 0.0513 AC: 544 AN: 10596

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

European-Non Finnish (NFE) AF: 0.0477 AC: 3241 AN: 68008

Other (OTH) AF: 0.0581 AC: 123 AN: 2116

Alfa AF: 0.0540 Hom.: 47

Bravo AF: 0.0686

Asia WGS AF: 0.179 AC: 621 AN: 3478

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	-0.77
CADD	Benign	15
DANN	Benign	0.64
PhyloP100		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2269381; hg19: chr22-51020069; COSMIC: COSV56414886; COSMIC: COSV56414886;