rs762677

Variant names:

• chr22-50579284-G-A
• rs762677
• NM_005198.5:c.1114-29C>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.1114-29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.077 in 1,609,802 control chromosomes in the GnomAD database, including 8,290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1169 hom., cov: 32)
  • Exomes 𝑓: 0.074 (7121 hom.)
• Consequence: CHKB NM_005198.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.33
• Publications: 6 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 22-50579284-G-A is Benign according to our data. Variant chr22-50579284-G-A is described in ClinVar as Benign. ClinVar VariationId is 1275585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 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.1114-29C>T		intron	N/A	NP_005189.2
	CHKB-CPT1B	NR_027928.2		n.1332-29C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHKB	ENST00000406938.3	TSL:1 MANE Select	c.1114-29C>T		intron	N/A	ENSP00000384400.3	Q9Y259-1
	CHKB-CPT1B	ENST00000453634.5	TSL:5	n.109-29C>T		intron	N/A	ENSP00000457031.1	H3BT56
	CHKB	ENST00000481673.5	TSL:1	n.1564-29C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15309 AN: 151972 Hom.: 1166 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0712

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0525

Gnomad OTH AF: 0.0839

GnomAD2 exomes AF: 0.120 AC: 29102 AN: 242458 AF XY: 0.115

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.201

Gnomad ASJ exome AF: 0.0521

Gnomad EAS exome AF: 0.413

Gnomad FIN exome AF: 0.0715

Gnomad NFE exome AF: 0.0527

Gnomad OTH exome AF: 0.0876

GnomAD4 exome AF: 0.0745 AC: 108567 AN: 1457712 Hom.: 7121 Cov.: 30 AF XY: 0.0759 AC XY: 55048 AN XY: 725172

African (AFR) AF: 0.146 AC: 4868 AN: 33356

American (AMR) AF: 0.191 AC: 8464 AN: 44252

Ashkenazi Jewish (ASJ) AF: 0.0532 AC: 1387 AN: 26072

East Asian (EAS) AF: 0.375 AC: 14828 AN: 39582

South Asian (SAS) AF: 0.139 AC: 11952 AN: 85864

European-Finnish (FIN) AF: 0.0687 AC: 3648 AN: 53102

Middle Eastern (MID) AF: 0.0578 AC: 333 AN: 5766

European-Non Finnish (NFE) AF: 0.0522 AC: 57885 AN: 1109480

Other (OTH) AF: 0.0864 AC: 5202 AN: 60238

GnomAD4 genome AF: 0.101 AC: 15343 AN: 152090 Hom.: 1169 Cov.: 32 AF XY: 0.105 AC XY: 7819 AN XY: 74342

African (AFR) AF: 0.143 AC: 5912 AN: 41460

American (AMR) AF: 0.128 AC: 1963 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0513 AC: 178 AN: 3472

East Asian (EAS) AF: 0.388 AC: 1999 AN: 5156

South Asian (SAS) AF: 0.158 AC: 758 AN: 4804

European-Finnish (FIN) AF: 0.0712 AC: 755 AN: 10608

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0525 AC: 3568 AN: 67994

Other (OTH) AF: 0.0863 AC: 182 AN: 2108

Alfa AF: 0.0706 Hom.: 113

Bravo AF: 0.108

Asia WGS AF: 0.252 AC: 877 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	2.7
DANN	Benign	0.74
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs762677; hg19: chr22-51017713; COSMIC: COSV56415516; COSMIC: COSV56415516;