rs80067609

Variant names:

• chr22-50582566-G-A
• rs80067609
• NM_005198.5:c.216C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-50582566-G-A
• chr22-50582566-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005198.5(CHKB):​c.216C>T​(p.Tyr72Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 1,609,032 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (96 hom., cov: 34)
  • Exomes 𝑓: 0.0018 (57 hom.)
• Consequence: CHKB NM_005198.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.749
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 22-50582566-G-A is Benign according to our data. Variant chr22-50582566-G-A is described in ClinVar as Benign. ClinVar VariationId is 128728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.749 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0553 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>T	p.Tyr72Tyr	synonymous	Exon 1 of 11	NP_005189.2
	CHKB-CPT1B	NR_027928.2		n.434C>T		non_coding_transcript_exon	Exon 1 of 30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHKB	ENST00000406938.3	TSL:1 MANE Select	c.216C>T	p.Tyr72Tyr	synonymous	Exon 1 of 11	ENSP00000384400.3	Q9Y259-1
	CHKB	ENST00000481673.5	TSL:1	n.280C>T		non_coding_transcript_exon	Exon 1 of 10
	CHKB	ENST00000939160.1		c.216C>T	p.Tyr72Tyr	synonymous	Exon 1 of 12	ENSP00000609219.1

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2523 AN: 152170 Hom.: 94 Cov.: 34

Gnomad AFR AF: 0.0571

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00416 AC: 965 AN: 232040 AF XY: 0.00319

Gnomad AFR exome AF: 0.0562

Gnomad AMR exome AF: 0.00354

Gnomad ASJ exome AF: 0.000105

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000503

Gnomad OTH exome AF: 0.00263

GnomAD4 exome AF: 0.00184 AC: 2687 AN: 1456746 Hom.: 57 Cov.: 32 AF XY: 0.00162 AC XY: 1173 AN XY: 724566

African (AFR) AF: 0.0552 AC: 1829 AN: 33142

American (AMR) AF: 0.00411 AC: 183 AN: 44494

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 25974

East Asian (EAS) AF: 0.00 AC: 0 AN: 39544

South Asian (SAS) AF: 0.0000582 AC: 5 AN: 85858

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51486

Middle Eastern (MID) AF: 0.00713 AC: 41 AN: 5750

European-Non Finnish (NFE) AF: 0.000361 AC: 401 AN: 1110380

Other (OTH) AF: 0.00378 AC: 227 AN: 60118

GnomAD4 genome AF: 0.0166 AC: 2534 AN: 152286 Hom.: 96 Cov.: 34 AF XY: 0.0165 AC XY: 1226 AN XY: 74460

African (AFR) AF: 0.0572 AC: 2379 AN: 41566

American (AMR) AF: 0.00654 AC: 100 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68014

Other (OTH) AF: 0.0123 AC: 26 AN: 2114

Alfa AF: 0.00368 Hom.: 2

Bravo AF: 0.0192

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000714

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Megaconial type congenital muscular dystrophy (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.94
PhyloP100		0.75
PromoterAI		0.064	Neutral
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs80067609; hg19: chr22-51020995;