Genetic Variant CKM:c.653+147C>A (chr19-45311602-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.14

Publications

11 publications found

Variant links:

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]

CKM links:

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ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001824.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKM	NM_001824.5	MANE Select	c.653+147C>A		intron	N/A	NP_001815.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKM	ENST00000221476.4	TSL:1 MANE Select	c.653+147C>A		intron	N/A	ENSP00000221476.2

Frequencies

GnomAD3 genomes

AF:

0.372

AC:

56476

AN:

151976

Hom.:

11209

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

6052

12105

18157

24210

30262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1614

3228

4842

6456

8070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.372

AC:

56507

AN:

152094

Hom.:

11220

Cov.:

AF XY:

0.368

AC XY:

27350

AN XY:

74362

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1782

3565

5347

7130

8912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.9

(source)

DANN

Benign

0.86

PhyloP100

2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over