rs7214723

Positions:

• chr17-3872554-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032294.3(CAMKK1):​c.1124A>G​(p.Glu375Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,610,876 control chromosomes in the GnomAD database, including 166,675 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.37 (11854 hom., cov: 33)
  • Exomes 𝑓: 0.45 (154821 hom.)
• Consequence: CAMKK1 NM_032294.3 missense, splice_region
• Scores: Splicing: ADA: 0.002102
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2780871E-5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMKK1	NM_032294.3	c.1124A>G	p.Glu375Gly	missense_variant, splice_region_variant	12/16	ENST00000348335.7	NP_115670.1
CAMKK1	NM_172206.2	c.1205A>G	p.Glu402Gly	missense_variant, splice_region_variant	12/16		NP_757343.2
CAMKK1	NM_172207.3	c.1238A>G	p.Glu413Gly	missense_variant, splice_region_variant	13/16		NP_757344.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMKK1	ENST00000348335.7	c.1124A>G	p.Glu375Gly	missense_variant, splice_region_variant	12/16	1	NM_032294.3	ENSP00000323118	P1
CAMKK1	ENST00000381769.6	c.1205A>G	p.Glu402Gly	missense_variant, splice_region_variant	12/16	1		ENSP00000371188
CAMKK1	ENST00000158166.5	c.1238A>G	p.Glu413Gly	missense_variant, splice_region_variant	13/16	1		ENSP00000158166

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56040 AN: 151890 Hom.: 11846 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.405

GnomAD3 exomes AF: 0.449 AC: 112747 AN: 251020 Hom.: 27116 AF XY: 0.459 AC XY: 62306 AN XY: 135660

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.567

Gnomad ASJ exome AF: 0.446

Gnomad EAS exome AF: 0.350

Gnomad SAS exome AF: 0.607

Gnomad FIN exome AF: 0.400

Gnomad NFE exome AF: 0.439

Gnomad OTH exome AF: 0.456

GnomAD4 exome AF: 0.455 AC: 663216 AN: 1458868 Hom.: 154821 Cov.: 33 AF XY: 0.459 AC XY: 333088 AN XY: 725950

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.562

Gnomad4 ASJ exome AF: 0.448

Gnomad4 EAS exome AF: 0.430

Gnomad4 SAS exome AF: 0.603

Gnomad4 FIN exome AF: 0.394

Gnomad4 NFE exome AF: 0.452

Gnomad4 OTH exome AF: 0.449

GnomAD4 genome AF: 0.369 AC: 56045 AN: 152008 Hom.: 11854 Cov.: 33 AF XY: 0.375 AC XY: 27892 AN XY: 74294

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.408

Alfa AF: 0.434 Hom.: 31128

Bravo AF: 0.363

TwinsUK AF: 0.447 AC: 1658

ALSPAC AF: 0.439 AC: 1691

ESP6500AA AF: 0.172 AC: 756

ESP6500EA AF: 0.446 AC: 3836

ExAC AF: 0.440 AC: 53369

Asia WGS AF: 0.541 AC: 1880 AN: 3478

EpiCase AF: 0.444

EpiControl AF: 0.452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	.;T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	0.017
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;D;T
MetaRNN	Benign	0.000013	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.82	.;L;.
MutationTaster	Benign	0.00029	P;P;P;P
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Benign	0.064
Sift	Benign	0.037	D;D;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.011	.;B;.
Vest4		0.11
MPC		0.49
ClinPred		0.029	T
GERP RS		4.1
Varity_R		0.23
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0021
dbscSNV1_RF	Benign	0.074
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

LitVar

Other links and lift over

dbSNP: rs7214723; hg19: chr17-3775848; COSMIC: COSV50113888;