rs432979

Positions:

• chr19-45318433-C-G

Variant summary

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

The NM_001824.5(CKM):​c.194-454G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 149,210 control chromosomes in the GnomAD database, including 3,117 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 0.18 (3117 hom., cov: 28)
• Consequence: CKM NM_001824.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CKM	NM_001824.5	c.194-454G>C		intron_variant		ENST00000221476.4	NP_001815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CKM	ENST00000221476.4	c.194-454G>C		intron_variant		1	NM_001824.5	ENSP00000221476.2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26259 AN: 149122 Hom.: 3106 Cov.: 28

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.0287

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.0716

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0892

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.176 AC: 26297 AN: 149210 Hom.: 3117 Cov.: 28 AF XY: 0.180 AC XY: 13103 AN XY: 72696

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.0716

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.0778

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.0892

Gnomad4 OTH AF: 0.151

Alfa AF: 0.140 Hom.: 274

Bravo AF: 0.186

Asia WGS AF: 0.174 AC: 605 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.30

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: rs432979; hg19: chr19-45821691;