19-45311602-G-T

Variant names:

• chr19-45311602-G-T
• rs7260463
• NM_001824.5:c.653+147C>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+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 NM_001824.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14
• Publications: 11 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=-0.83).
• 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 rank	MANE	Protein	UniProt
CKM	NM_001824.5	c.653+147C>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+147C>A		intron_variant	Intron 5 of 7	1	NM_001824.5	ENSP00000221476.2

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

African (AFR) AF: 0.499 AC: 7282 AN: 14596

American (AMR) AF: 0.198 AC: 4595 AN: 23260

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 5002 AN: 14930

East Asian (EAS) AF: 0.0938 AC: 2966 AN: 31616

South Asian (SAS) AF: 0.388 AC: 19137 AN: 49362

European-Finnish (FIN) AF: 0.347 AC: 10338 AN: 29820

Middle Eastern (MID) AF: 0.367 AC: 799 AN: 2176

European-Non Finnish (NFE) AF: 0.341 AC: 119644 AN: 350378

Other (OTH) AF: 0.340 AC: 9946 AN: 29270

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

African (AFR) AF: 0.503 AC: 20861 AN: 41486

American (AMR) AF: 0.257 AC: 3922 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1153 AN: 3472

East Asian (EAS) AF: 0.111 AC: 576 AN: 5174

South Asian (SAS) AF: 0.395 AC: 1908 AN: 4826

European-Finnish (FIN) AF: 0.342 AC: 3620 AN: 10572

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23241 AN: 67978

Other (OTH) AF: 0.352 AC: 742 AN: 2110

Alfa AF: 0.346 Hom.: 28894

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
PhyloP100		2.1
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: rs7260463; hg19: chr19-45814860;