Genetic Variant CKM:p.Ile373Ile (chr19-45306777-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001824.5(CKM):c.1119T>C(p.Ile373Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 1,613,892 control chromosomes in the GnomAD database, including 395,059 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 0.71 ( 39149 hom., cov: 32)

Exomes 𝑓: 0.69 ( 355910 hom. )

Consequence

CKM
NM_001824.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.654

Publications

42 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP7

Synonymous conserved (PhyloP=0.654 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CKM	NM_001824.5 link	c.1119T>C	p.Ile373Ile	synonymous_variant	Exon 8 of 8	ENST00000221476.4	NP_001815.2	P06732B2R892

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CKM	ENST00000221476.4 link	c.1119T>C	p.Ile373Ile	synonymous_variant	Exon 8 of 8	1	NM_001824.5	ENSP00000221476.2		P06732

Frequencies

GnomAD3 genomes

AF:

0.705

AC:

107178

AN:

151950

Hom.:

39109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.815

Gnomad AMI

AF:

0.784

Gnomad AMR

AF:

0.501

Gnomad ASJ

AF:

0.667

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.670

Gnomad FIN

AF:

0.752

Gnomad MID

AF:

0.640

Gnomad NFE

AF:

0.717

Gnomad OTH

AF:

0.673

GnomAD2 exomes

AF:

0.632

AC:

158798

AN:

251458

AF XY:

0.645

show subpopulations

Gnomad AFR exome

AF:

0.817

Gnomad AMR exome

AF:

0.360

Gnomad ASJ exome

AF:

0.678

Gnomad EAS exome

AF:

0.237

Gnomad FIN exome

AF:

0.748

Gnomad NFE exome

AF:

0.712

Gnomad OTH exome

AF:

0.655

GnomAD4 exome

AF:

0.690

AC:

1008783

AN:

1461824

Hom.:

355910

Cov.:

AF XY:

0.692

AC XY:

502968

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.814

AC:

27263

AN:

33480

American (AMR)

AF:

0.376

AC:

16830

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.669

AC:

17485

AN:

26136

East Asian (EAS)

AF:

0.242

AC:

9625

AN:

39700

South Asian (SAS)

AF:

0.680

AC:

58629

AN:

86256

European-Finnish (FIN)

AF:

0.739

AC:

39480

AN:

53402

Middle Eastern (MID)

AF:

0.634

AC:

3658

AN:

5768

European-Non Finnish (NFE)

AF:

0.715

AC:

794823

AN:

1111964

Other (OTH)

AF:

0.679

AC:

40990

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

18170

36339

54509

72678

90848

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19632

39264

58896

78528

98160

<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:

0.705

AC:

107268

AN:

152068

Hom.:

39149

Cov.:

AF XY:

0.700

AC XY:

52034

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.815

AC:

33831

AN:

41508

American (AMR)

AF:

0.500

AC:

7637

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.667

AC:

2312

AN:

3468

East Asian (EAS)

AF:

0.241

AC:

1236

AN:

5138

South Asian (SAS)

AF:

0.670

AC:

3231

AN:

4824

European-Finnish (FIN)

AF:

0.752

AC:

7965

AN:

10588

Middle Eastern (MID)

AF:

0.644

AC:

188

AN:

292

European-Non Finnish (NFE)

AF:

0.717

AC:

48732

AN:

67954

Other (OTH)

AF:

0.674

AC:

1423

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1492

2984

4476

5968

7460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<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:

0.696

Hom.:

120368

Bravo

AF:

0.685

Asia WGS

AF:

0.503

AC:

1754

AN:

3478

EpiCase

AF:

0.713

EpiControl

AF:

0.699

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.1

(source)

DANN

Benign

0.85

PhyloP100

0.65

Mutation Taster

=99/1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over