rs7260463

Positions:

• chr19-45311602-G-T

Variant summary

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

The ENST00000221476.4(CKM):​c.653+147C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 697,502 control chromosomes in the GnomAD database, including 42,331 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 0.37 (11220 hom., cov: 32)
  • Exomes 𝑓: 0.33 (31111 hom.)
• Consequence: CKM ENST00000221476.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CKM	NM_001824.5	c.653+147C>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+147C>A		intron_variant		1	NM_001824.5	ENSP00000221476	P1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56476 AN: 151976 Hom.: 11209 Cov.: 32

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.329 AC: 179709 AN: 545408 Hom.: 31111 AF XY: 0.331 AC XY: 93968 AN XY: 283606

Gnomad4 AFR exome AF: 0.499

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.335

Gnomad4 EAS exome AF: 0.0938

Gnomad4 SAS exome AF: 0.388

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.340

GnomAD4 genome AF: 0.372 AC: 56507 AN: 152094 Hom.: 11220 Cov.: 32 AF XY: 0.368 AC XY: 27350 AN XY: 74362

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.352

Alfa AF: 0.342 Hom.: 12002

Bravo AF: 0.366

Asia WGS AF: 0.281 AC: 982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.86

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: rs7260463; hg19: chr19-45814860;