19-45322222-C-G

Variant names:

• chr19-45322222-C-G
• rs10410448
• NM_001824.5:c.-19+599G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001824.5(CKM):​c.-19+599G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 150,830 control chromosomes in the GnomAD database, including 17,770 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (17770 hom., cov: 26)
• Consequence: CKM NM_001824.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 4 publications found

Genes affected

CKM (HGNC:1994): (creatine kinase, M-type) The protein encoded by this gene is a cytoplasmic enzyme involved in energy homeostasis and is an important serum marker for myocardial infarction. The encoded protein reversibly catalyzes the transfer of phosphate between ATP and various phosphogens such as creatine phosphate. It acts as a homodimer in striated muscle as well as in other tissues, and as a heterodimer with a similar brain isozyme in heart. The encoded protein is a member of the ATP:guanido phosphotransferase protein family. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001824.5. 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
	CKM	NM_001824.5	MANE Select	c.-19+599G>C		intron	N/A	NP_001815.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKM	ENST00000221476.4	TSL:1 MANE Select	c.-19+599G>C		intron	N/A	ENSP00000221476.2
	CKM	ENST00000969560.1		c.-19+599G>C		intron	N/A	ENSP00000639619.1
	CKM	ENST00000969562.1		c.-19+599G>C		intron	N/A	ENSP00000639621.1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 68534 AN: 150716 Hom.: 17764 Cov.: 26

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.0744

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.443

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.455 AC: 68576 AN: 150830 Hom.: 17770 Cov.: 26 AF XY: 0.450 AC XY: 33151 AN XY: 73592

African (AFR) AF: 0.701 AC: 28612 AN: 40844

American (AMR) AF: 0.311 AC: 4718 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1545 AN: 3466

East Asian (EAS) AF: 0.0736 AC: 379 AN: 5146

South Asian (SAS) AF: 0.452 AC: 2133 AN: 4720

European-Finnish (FIN) AF: 0.390 AC: 4078 AN: 10458

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.380 AC: 25755 AN: 67702

Other (OTH) AF: 0.441 AC: 926 AN: 2098

Alfa AF: 0.285 Hom.: 764

Bravo AF: 0.452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.2
DANN	Benign	0.61
PhyloP100		-1.6
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: rs10410448; hg19: chr19-45825480;