NM_001824.5:c.1119T>C

Variant names:

• chr19-45306777-A-G
• rs4884
• NM_001824.5:c.1119T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001824.5(CKM):​c.1119T>C​(p.Ile373Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 1,613,892 control chromosomes in the GnomAD database, including 395,059 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 0.71 (39149 hom., cov: 32)
  • Exomes 𝑓: 0.69 (355910 hom.)
• Consequence: CKM NM_001824.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.654
• Publications: 42 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=0.654 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKM	NM_001824.5	MANE Select	c.1119T>C	p.Ile373Ile	synonymous	Exon 8 of 8	NP_001815.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKM	ENST00000221476.4	TSL:1 MANE Select	c.1119T>C	p.Ile373Ile	synonymous	Exon 8 of 8	ENSP00000221476.2	P06732
	CKM	ENST00000969560.1		c.1272T>C	p.Ile424Ile	synonymous	Exon 8 of 8	ENSP00000639619.1
	CKM	ENST00000969562.1		c.1236T>C	p.Ile412Ile	synonymous	Exon 9 of 9	ENSP00000639621.1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107178 AN: 151950 Hom.: 39109 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.673

GnomAD2 exomes AF: 0.632 AC: 158798 AN: 251458 AF XY: 0.645

Gnomad AFR exome AF: 0.817

Gnomad AMR exome AF: 0.360

Gnomad ASJ exome AF: 0.678

Gnomad EAS exome AF: 0.237

Gnomad FIN exome AF: 0.748

Gnomad NFE exome AF: 0.712

Gnomad OTH exome AF: 0.655

GnomAD4 exome AF: 0.690 AC: 1008783 AN: 1461824 Hom.: 355910 Cov.: 63 AF XY: 0.692 AC XY: 502968 AN XY: 727214

African (AFR) AF: 0.814 AC: 27263 AN: 33480

American (AMR) AF: 0.376 AC: 16830 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 17485 AN: 26136

East Asian (EAS) AF: 0.242 AC: 9625 AN: 39700

South Asian (SAS) AF: 0.680 AC: 58629 AN: 86256

European-Finnish (FIN) AF: 0.739 AC: 39480 AN: 53402

Middle Eastern (MID) AF: 0.634 AC: 3658 AN: 5768

European-Non Finnish (NFE) AF: 0.715 AC: 794823 AN: 1111964

Other (OTH) AF: 0.679 AC: 40990 AN: 60394

GnomAD4 genome AF: 0.705 AC: 107268 AN: 152068 Hom.: 39149 Cov.: 32 AF XY: 0.700 AC XY: 52034 AN XY: 74328

African (AFR) AF: 0.815 AC: 33831 AN: 41508

American (AMR) AF: 0.500 AC: 7637 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2312 AN: 3468

East Asian (EAS) AF: 0.241 AC: 1236 AN: 5138

South Asian (SAS) AF: 0.670 AC: 3231 AN: 4824

European-Finnish (FIN) AF: 0.752 AC: 7965 AN: 10588

Middle Eastern (MID) AF: 0.644 AC: 188 AN: 292

European-Non Finnish (NFE) AF: 0.717 AC: 48732 AN: 67954

Other (OTH) AF: 0.674 AC: 1423 AN: 2110

Alfa AF: 0.696 Hom.: 120368

Bravo AF: 0.685

Asia WGS AF: 0.503 AC: 1754 AN: 3478

EpiCase AF: 0.713

EpiControl AF: 0.699

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.1
DANN	Benign	0.85
PhyloP100		0.65
Mutation Taster		=99/1	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: rs4884; hg19: chr19-45810035; COSMIC: COSV53464538; COSMIC: COSV53464538;