19-45311650-C-T

Position:

• chr19-45311650-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001824.5(CKM):​c.653+99G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 967,558 control chromosomes in the GnomAD database, including 119,994 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 0.55 (24978 hom., cov: 31)
  • Exomes 𝑓: 0.47 (95016 hom.)
• Consequence: CKM NM_001824.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.891

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CKM	NM_001824.5	c.653+99G>A		intron_variant		ENST00000221476.4	NP_001815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CKM	ENST00000221476.4	c.653+99G>A		intron_variant		1	NM_001824.5	ENSP00000221476.2

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83176 AN: 151744 Hom.: 24939 Cov.: 31

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.544

GnomAD4 exome AF: 0.470 AC: 383520 AN: 815696 Hom.: 95016 AF XY: 0.472 AC XY: 195593 AN XY: 414408

Gnomad4 AFR exome AF: 0.783

Gnomad4 AMR exome AF: 0.288

Gnomad4 ASJ exome AF: 0.482

Gnomad4 EAS exome AF: 0.0945

Gnomad4 SAS exome AF: 0.525

Gnomad4 FIN exome AF: 0.501

Gnomad4 NFE exome AF: 0.481

Gnomad4 OTH exome AF: 0.480

GnomAD4 genome AF: 0.548 AC: 83251 AN: 151862 Hom.: 24978 Cov.: 31 AF XY: 0.544 AC XY: 40333 AN XY: 74196

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.539

Alfa AF: 0.514 Hom.: 6899

Bravo AF: 0.543

Asia WGS AF: 0.343 AC: 1198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.80
DANN	Benign	0.49

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: rs7260359; hg19: chr19-45814908;