rs140514

Variant names:

• chr22-50580150-A-G
• rs140514
• NM_005198.5:c.818+40T>C

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.818+40T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 1,612,786 control chromosomes in the GnomAD database, including 177,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (12823 hom., cov: 33)
  • Exomes 𝑓: 0.47 (164367 hom.)
• Consequence: CHKB NM_005198.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.183
• Publications: 16 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=-0.91).
• BP6: Variant 22-50580150-A-G is Benign according to our data. Variant chr22-50580150-A-G is described in ClinVar as Benign. ClinVar VariationId is 1294337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 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.818+40T>C		intron	N/A	NP_005189.2
	CHKB-CPT1B	NR_027928.2		n.1036+40T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHKB	ENST00000406938.3	TSL:1 MANE Select	c.818+40T>C		intron	N/A	ENSP00000384400.3
	CHKB	ENST00000481673.5	TSL:1	n.1268+40T>C		intron	N/A
	CHKB	ENST00000464225.5	TSL:2	n.64+40T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58230 AN: 152062 Hom.: 12828 Cov.: 33

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.392

GnomAD2 exomes AF: 0.444 AC: 110870 AN: 249564 AF XY: 0.445

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.464

Gnomad ASJ exome AF: 0.450

Gnomad EAS exome AF: 0.466

Gnomad FIN exome AF: 0.529

Gnomad NFE exome AF: 0.484

Gnomad OTH exome AF: 0.452

GnomAD4 exome AF: 0.470 AC: 686023 AN: 1460604 Hom.: 164367 Cov.: 35 AF XY: 0.467 AC XY: 339141 AN XY: 726632

African (AFR) AF: 0.135 AC: 4512 AN: 33466

American (AMR) AF: 0.463 AC: 20723 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 11543 AN: 26132

East Asian (EAS) AF: 0.474 AC: 18814 AN: 39696

South Asian (SAS) AF: 0.368 AC: 31731 AN: 86200

European-Finnish (FIN) AF: 0.521 AC: 27670 AN: 53142

Middle Eastern (MID) AF: 0.352 AC: 2025 AN: 5746

European-Non Finnish (NFE) AF: 0.488 AC: 542374 AN: 1111168

Other (OTH) AF: 0.441 AC: 26631 AN: 60332

GnomAD4 genome AF: 0.383 AC: 58231 AN: 152182 Hom.: 12823 Cov.: 33 AF XY: 0.386 AC XY: 28702 AN XY: 74392

African (AFR) AF: 0.148 AC: 6137 AN: 41530

American (AMR) AF: 0.434 AC: 6637 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1531 AN: 3470

East Asian (EAS) AF: 0.470 AC: 2431 AN: 5172

South Asian (SAS) AF: 0.362 AC: 1745 AN: 4820

European-Finnish (FIN) AF: 0.527 AC: 5585 AN: 10588

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32763 AN: 67994

Other (OTH) AF: 0.389 AC: 823 AN: 2114

Alfa AF: 0.438 Hom.: 36510

Bravo AF: 0.372

Asia WGS AF: 0.368 AC: 1280 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.56
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs140514; hg19: chr22-51018579; COSMIC: COSV56414928; COSMIC: COSV56414928;