19-45322368-A-T

Variant names:

• chr19-45322368-A-T
• rs344816
• NM_001824.5:c.-19+453T>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.-19+453T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 152,074 control chromosomes in the GnomAD database, including 26,944 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 0.56 (26944 hom., cov: 31)
• Consequence: CKM NM_001824.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CKM	NM_001824.5	c.-19+453T>A		intron_variant	Intron 1 of 7	ENST00000221476.4	NP_001815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CKM	ENST00000221476.4	c.-19+453T>A		intron_variant	Intron 1 of 7	1	NM_001824.5	ENSP00000221476.2

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84752 AN: 151956 Hom.: 26920 Cov.: 31

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.0758

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.558 AC: 84824 AN: 152074 Hom.: 26944 Cov.: 31 AF XY: 0.554 AC XY: 41212 AN XY: 74338

African (AFR) AF: 0.852 AC: 35339 AN: 41498

American (AMR) AF: 0.363 AC: 5546 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1749 AN: 3470

East Asian (EAS) AF: 0.0750 AC: 388 AN: 5174

South Asian (SAS) AF: 0.495 AC: 2387 AN: 4822

European-Finnish (FIN) AF: 0.553 AC: 5844 AN: 10576

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31968 AN: 67946

Other (OTH) AF: 0.536 AC: 1127 AN: 2104

Alfa AF: 0.419 Hom.: 1488

Bravo AF: 0.549

Asia WGS AF: 0.327 AC: 1144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.81
PhyloP100		-0.45
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: rs344816; hg19: chr19-45825626;