19-45311650-C-T

Variant names:

• chr19-45311650-C-T
• rs7260359
• NM_001824.5:c.653+99G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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 -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 rank	MANE	Protein	UniProt
CKM	NM_001824.5	c.653+99G>A		intron_variant	Intron 5 of 7	ENST00000221476.4	NP_001815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CKM	ENST00000221476.4	c.653+99G>A		intron_variant	Intron 5 of 7	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

African (AFR) AF: 0.783 AC: 15710 AN: 20058

American (AMR) AF: 0.288 AC: 8140 AN: 28256

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 8560 AN: 17762

East Asian (EAS) AF: 0.0945 AC: 3119 AN: 33012

South Asian (SAS) AF: 0.525 AC: 30736 AN: 58580

European-Finnish (FIN) AF: 0.501 AC: 15630 AN: 31180

Middle Eastern (MID) AF: 0.550 AC: 1633 AN: 2970

European-Non Finnish (NFE) AF: 0.481 AC: 281512 AN: 585404

Other (OTH) AF: 0.480 AC: 18480 AN: 38474

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

African (AFR) AF: 0.781 AC: 32378 AN: 41444

American (AMR) AF: 0.385 AC: 5861 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1656 AN: 3466

East Asian (EAS) AF: 0.113 AC: 584 AN: 5160

South Asian (SAS) AF: 0.516 AC: 2479 AN: 4804

European-Finnish (FIN) AF: 0.499 AC: 5258 AN: 10538

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33321 AN: 67908

Other (OTH) AF: 0.539 AC: 1139 AN: 2112

Alfa AF: 0.540 Hom.: 21504

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
PhyloP100		-0.89
Mutation Taster		=100/0	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: rs7260359; hg19: chr19-45814908;