chr22-50578965-G-C

Variant names:

• chr22-50578965-G-C
• rs3180872
• NM_005198.5:c.*216C>G

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.*216C>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0956 in 608,108 control chromosomes in the GnomAD database, including 5,013 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1191 hom., cov: 32)
  • Exomes 𝑓: 0.094 (3822 hom.)
• Consequence: CHKB NM_005198.5 splice_region
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.85
• Publications: 11 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=-0.93).
• BP6: Variant 22-50578965-G-C is Benign according to our data. Variant chr22-50578965-G-C is described in ClinVar as Benign. ClinVar VariationId is 342160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 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.*216C>G		splice_region	Exon 11 of 11	NP_005189.2
	CHKB	NM_005198.5	MANE Select	c.*216C>G		3_prime_UTR	Exon 11 of 11	NP_005189.2
	CHKB-CPT1B	NR_027928.2		n.1551+71C>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.*216C>G		splice_region	Exon 11 of 11	ENSP00000384400.3	Q9Y259-1
	CHKB	ENST00000406938.3	TSL:1 MANE Select	c.*216C>G		3_prime_UTR	Exon 11 of 11	ENSP00000384400.3	Q9Y259-1
	CHKB	ENST00000481673.5	TSL:1	n.1854C>G		splice_region non_coding_transcript_exon	Exon 10 of 10

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15369 AN: 152084 Hom.: 1188 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: 0.397

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0712

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0526

Gnomad OTH AF: 0.0835

GnomAD4 exome AF: 0.0938 AC: 42748 AN: 455906 Hom.: 3822 Cov.: 4 AF XY: 0.0956 AC XY: 23137 AN XY: 242052

African (AFR) AF: 0.144 AC: 1863 AN: 12914

American (AMR) AF: 0.171 AC: 3907 AN: 22814

Ashkenazi Jewish (ASJ) AF: 0.0518 AC: 729 AN: 14068

East Asian (EAS) AF: 0.373 AC: 11280 AN: 30230

South Asian (SAS) AF: 0.137 AC: 6579 AN: 47892

European-Finnish (FIN) AF: 0.0666 AC: 2095 AN: 31476

Middle Eastern (MID) AF: 0.0672 AC: 131 AN: 1948

European-Non Finnish (NFE) AF: 0.0517 AC: 13904 AN: 268840

Other (OTH) AF: 0.0879 AC: 2260 AN: 25724

GnomAD4 genome AF: 0.101 AC: 15405 AN: 152202 Hom.: 1191 Cov.: 32 AF XY: 0.106 AC XY: 7865 AN XY: 74424

African (AFR) AF: 0.142 AC: 5905 AN: 41518

American (AMR) AF: 0.129 AC: 1967 AN: 15290

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

East Asian (EAS) AF: 0.398 AC: 2054 AN: 5162

South Asian (SAS) AF: 0.157 AC: 756 AN: 4818

European-Finnish (FIN) AF: 0.0712 AC: 755 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0526 AC: 3581 AN: 68020

Other (OTH) AF: 0.0859 AC: 181 AN: 2106

Alfa AF: 0.0731 Hom.: 97

Bravo AF: 0.109

Asia WGS AF: 0.257 AC: 894 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.93
CADD	Benign	0.13
DANN	Benign	0.78
PhyloP100		-1.8
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)		0.0		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: rs3180872; hg19: chr22-51017394;