rs4884

Positions:

• chr19-45306777-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000221476.4(CKM):​c.1119T>C​(p.Ile373=) 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 ENST00000221476.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.654

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CKM	NM_001824.5	c.1119T>C	p.Ile373=	synonymous_variant	8/8	ENST00000221476.4	NP_001815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CKM	ENST00000221476.4	c.1119T>C	p.Ile373=	synonymous_variant	8/8	1	NM_001824.5	ENSP00000221476	P1

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

GnomAD3 exomes AF: 0.632 AC: 158798 AN: 251458 Hom.: 54110 AF XY: 0.645 AC XY: 87591 AN XY: 135902

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 SAS exome AF: 0.675

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

Gnomad4 AFR exome AF: 0.814

Gnomad4 AMR exome AF: 0.376

Gnomad4 ASJ exome AF: 0.669

Gnomad4 EAS exome AF: 0.242

Gnomad4 SAS exome AF: 0.680

Gnomad4 FIN exome AF: 0.739

Gnomad4 NFE exome AF: 0.715

Gnomad4 OTH exome AF: 0.679

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

Gnomad4 AFR AF: 0.815

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.674

Alfa AF: 0.693 Hom.: 79198

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.1
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs4884; hg19: chr19-45810035; COSMIC: COSV53464538; COSMIC: COSV53464538;