22-50579085-C-G

Variant names:

• chr22-50579085-C-G
• rs17001634
• NM_005198.5:c.*96G>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.*96G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 1,231,266 control chromosomes in the GnomAD database, including 1,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (195 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1452 hom.)
• Consequence: CHKB NM_005198.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.182
• Publications: 3 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=-0.62).
• BP6: Variant 22-50579085-C-G is Benign according to our data. Variant chr22-50579085-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 342164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 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.*96G>C		3_prime_UTR	Exon 11 of 11	NP_005189.2
	CHKB-CPT1B	NR_027928.2		n.1502G>C		non_coding_transcript_exon	Exon 11 of 30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHKB	ENST00000406938.3	TSL:1 MANE Select	c.*96G>C		3_prime_UTR	Exon 11 of 11	ENSP00000384400.3	Q9Y259-1
	CHKB-CPT1B	ENST00000453634.5	TSL:5	n.*96G>C		non_coding_transcript_exon	Exon 3 of 23	ENSP00000457031.1	H3BT56
	CHKB	ENST00000481673.5	TSL:1	n.1734G>C		non_coding_transcript_exon	Exon 10 of 10

Frequencies

GnomAD3 genomes AF: 0.0355 AC: 5401 AN: 152182 Hom.: 197 Cov.: 32

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.0755

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0388

GnomAD4 exome AF: 0.0369 AC: 39767 AN: 1078966 Hom.: 1452 Cov.: 15 AF XY: 0.0400 AC XY: 21844 AN XY: 546558

African (AFR) AF: 0.0111 AC: 280 AN: 25314

American (AMR) AF: 0.0803 AC: 2856 AN: 35566

Ashkenazi Jewish (ASJ) AF: 0.0335 AC: 777 AN: 23170

East Asian (EAS) AF: 0.112 AC: 3853 AN: 34402

South Asian (SAS) AF: 0.128 AC: 9341 AN: 72980

European-Finnish (FIN) AF: 0.0520 AC: 2525 AN: 48600

Middle Eastern (MID) AF: 0.0542 AC: 257 AN: 4740

European-Non Finnish (NFE) AF: 0.0229 AC: 18037 AN: 786754

Other (OTH) AF: 0.0388 AC: 1841 AN: 47440

GnomAD4 genome AF: 0.0355 AC: 5408 AN: 152300 Hom.: 195 Cov.: 32 AF XY: 0.0407 AC XY: 3034 AN XY: 74458

African (AFR) AF: 0.0107 AC: 446 AN: 41576

American (AMR) AF: 0.0754 AC: 1153 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 107 AN: 3470

East Asian (EAS) AF: 0.107 AC: 556 AN: 5180

South Asian (SAS) AF: 0.135 AC: 653 AN: 4826

European-Finnish (FIN) AF: 0.0586 AC: 622 AN: 10614

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0255 AC: 1735 AN: 68018

Other (OTH) AF: 0.0393 AC: 83 AN: 2112

Alfa AF: 0.0284 Hom.: 14

Bravo AF: 0.0325

Asia WGS AF: 0.130 AC: 449 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Megaconial type congenital muscular dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.4
DANN	Benign	0.79
PhyloP100		0.18
Mutation Taster		=298/2	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: rs17001634; hg19: chr22-51017514; COSMIC: COSV107345032; COSMIC: COSV107345032;