rs1056964

Variant names:

• chr22-50579047-A-G
• rs1056964
• NM_005198.5:c.*134T>C

Your query was ambiguous. Multiple possible variants found:

• chr22-50579047-A-G
• chr22-50579047-A-C
• chr22-50579047-A-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.*134T>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 0.0898 in 847,002 control chromosomes in the GnomAD database, including 6,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1210 hom., cov: 32)
  • Exomes 𝑓: 0.087 (4912 hom.)
• Consequence: CHKB NM_005198.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.23
• Publications: 10 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 22-50579047-A-G is Benign according to our data. Variant chr22-50579047-A-G is described in ClinVar as Benign. ClinVar VariationId is 342162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 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.*134T>C		3_prime_UTR	Exon 11 of 11	NP_005189.2
	CHKB-CPT1B	NR_027928.2		n.1540T>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.*134T>C		3_prime_UTR	Exon 11 of 11	ENSP00000384400.3	Q9Y259-1
	CHKB-CPT1B	ENST00000453634.5	TSL:5	n.*134T>C		non_coding_transcript_exon	Exon 3 of 23	ENSP00000457031.1	H3BT56
	CHKB	ENST00000481673.5	TSL:1	n.1772T>C		non_coding_transcript_exon	Exon 10 of 10

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15424 AN: 152110 Hom.: 1207 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0713

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0526

Gnomad OTH AF: 0.0832

GnomAD4 exome AF: 0.0872 AC: 60592 AN: 694774 Hom.: 4912 Cov.: 9 AF XY: 0.0887 AC XY: 32414 AN XY: 365472

African (AFR) AF: 0.148 AC: 2653 AN: 17974

American (AMR) AF: 0.182 AC: 6272 AN: 34454

Ashkenazi Jewish (ASJ) AF: 0.0536 AC: 1093 AN: 20386

East Asian (EAS) AF: 0.379 AC: 12283 AN: 32446

South Asian (SAS) AF: 0.137 AC: 8813 AN: 64310

European-Finnish (FIN) AF: 0.0681 AC: 3194 AN: 46916

Middle Eastern (MID) AF: 0.0636 AC: 197 AN: 3096

European-Non Finnish (NFE) AF: 0.0522 AC: 23001 AN: 440616

Other (OTH) AF: 0.0893 AC: 3086 AN: 34576

GnomAD4 genome AF: 0.102 AC: 15458 AN: 152228 Hom.: 1210 Cov.: 32 AF XY: 0.106 AC XY: 7895 AN XY: 74444

African (AFR) AF: 0.143 AC: 5920 AN: 41526

American (AMR) AF: 0.129 AC: 1972 AN: 15296

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

East Asian (EAS) AF: 0.402 AC: 2081 AN: 5176

South Asian (SAS) AF: 0.158 AC: 762 AN: 4822

European-Finnish (FIN) AF: 0.0713 AC: 757 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0526 AC: 3579 AN: 68004

Other (OTH) AF: 0.0856 AC: 181 AN: 2114

Alfa AF: 0.0672 Hom.: 246

Bravo AF: 0.109

Asia WGS AF: 0.256 AC: 891 AN: 3478

ClinVar

ClinVar submissions

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	1.6
DANN	Benign	0.52
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1056964; hg19: chr22-51017476;