Genetic Variant CAMKK1:c.463-133C>T (chr17-3883613-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_032294.3(CAMKK1):c.463-133C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 842,248 control chromosomes in the GnomAD database, including 49,239 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 0.34 ( 9071 hom., cov: 32)

Exomes 𝑓: 0.34 ( 40168 hom. )

Consequence

CAMKK1
NM_032294.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.557

Publications

16 publications found

Variant links:

Genes affected

CAMKK1 (HGNC:1469): (calcium/calmodulin dependent protein kinase kinase 1) The product of this gene belongs to the Serine/Threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. This protein plays a role in the calcium/calmodulin-dependent (CaM) kinase cascade. Three transcript variants encoding two distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

CAMKK1 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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032294.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CAMKK1	NM_032294.3	MANE Select	c.463-133C>T	intron	N/A	NP_115670.1
CAMKK1	NM_172206.2		c.544-133C>T	intron	N/A	NP_757343.2
CAMKK1	NM_172207.3		c.463-133C>T	intron	N/A	NP_757344.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CAMKK1	ENST00000348335.7	TSL:1 MANE Select	c.463-133C>T	intron	N/A	ENSP00000323118.3
CAMKK1	ENST00000381769.6	TSL:1	c.544-133C>T	intron	N/A	ENSP00000371188.2
CAMKK1	ENST00000158166.5	TSL:1	c.463-133C>T	intron	N/A	ENSP00000158166.5

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51699

AN:

151780

Hom.:

9056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.367

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.325

Gnomad ASJ

AF:

0.334

Gnomad EAS

AF:

0.131

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.345

GnomAD4 exome

AF:

0.336

AC:

231888

AN:

690350

Hom.:

40168

AF XY:

0.334

AC XY:

123082

AN XY:

368418

show subpopulations

African (AFR)

AF:

0.370

AC:

7015

AN:

18960

American (AMR)

AF:

0.302

AC:

11999

AN:

39774

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

6649

AN:

19644

East Asian (EAS)

AF:

0.145

AC:

5238

AN:

36056

South Asian (SAS)

AF:

0.296

AC:

19651

AN:

66432

European-Finnish (FIN)

AF:

0.299

AC:

13990

AN:

46826

Middle Eastern (MID)

AF:

0.390

AC:

1501

AN:

3850

European-Non Finnish (NFE)

AF:

0.363

AC:

153857

AN:

423816

Other (OTH)

AF:

0.343

AC:

11988

AN:

34992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

7837

15674

23510

31347

39184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2116

4232

6348

8464

10580

<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:

0.341

AC:

51747

AN:

151898

Hom.:

9071

Cov.:

AF XY:

0.335

AC XY:

24839

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.368

AC:

15215

AN:

41390

American (AMR)

AF:

0.325

AC:

4962

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

1159

AN:

3466

East Asian (EAS)

AF:

0.131

AC:

676

AN:

5172

South Asian (SAS)

AF:

0.292

AC:

1410

AN:

4822

European-Finnish (FIN)

AF:

0.292

AC:

3080

AN:

10562

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.356

AC:

24202

AN:

67904

Other (OTH)

AF:

0.345

AC:

728

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1731

3462

5193

6924

8655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.350

Hom.:

23913

Bravo

AF:

0.343

Asia WGS

AF:

0.226

AC:

789

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.4

(source)

DANN

Benign

0.61

PhyloP100

0.56

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