rs7214723

Variant names:

• chr17-3872554-T-C
• rs7214723
• NM_032294.3:c.1124A>G

Variant summary

Our verdict is Benign. The variant received -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. 15/23 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.

• 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
• Publications: 48 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CAMKK1	NM_032294.3	c.1124A>G	p.Glu375Gly	missense_variant, splice_region_variant	Exon 12 of 16	ENST00000348335.7	NP_115670.1
CAMKK1	NM_172206.2	c.1205A>G	p.Glu402Gly	missense_variant, splice_region_variant	Exon 12 of 16		NP_757343.2
CAMKK1	NM_172207.3	c.1238A>G	p.Glu413Gly	missense_variant, splice_region_variant	Exon 13 of 16		NP_757344.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMKK1	ENST00000348335.7	c.1124A>G	p.Glu375Gly	missense_variant, splice_region_variant	Exon 12 of 16	1	NM_032294.3	ENSP00000323118.3
CAMKK1	ENST00000381769.6	c.1205A>G	p.Glu402Gly	missense_variant, splice_region_variant	Exon 12 of 16	1		ENSP00000371188.2
CAMKK1	ENST00000158166.5	c.1238A>G	p.Glu413Gly	missense_variant, splice_region_variant	Exon 13 of 16	1		ENSP00000158166.5

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

GnomAD2 exomes AF: 0.449 AC: 112747 AN: 251020 AF XY: 0.459

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 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

African (AFR) AF: 0.144 AC: 4816 AN: 33452

American (AMR) AF: 0.562 AC: 25135 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 11690 AN: 26116

East Asian (EAS) AF: 0.430 AC: 17066 AN: 39676

South Asian (SAS) AF: 0.603 AC: 52001 AN: 86168

European-Finnish (FIN) AF: 0.394 AC: 21038 AN: 53382

Middle Eastern (MID) AF: 0.478 AC: 2753 AN: 5764

European-Non Finnish (NFE) AF: 0.452 AC: 501640 AN: 1109314

Other (OTH) AF: 0.449 AC: 27077 AN: 60308

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

African (AFR) AF: 0.163 AC: 6779 AN: 41500

American (AMR) AF: 0.498 AC: 7605 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1567 AN: 3466

East Asian (EAS) AF: 0.376 AC: 1937 AN: 5146

South Asian (SAS) AF: 0.618 AC: 2973 AN: 4808

European-Finnish (FIN) AF: 0.396 AC: 4181 AN: 10568

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29745 AN: 67922

Other (OTH) AF: 0.408 AC: 863 AN: 2114

Alfa AF: 0.420 Hom.: 41872

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;.
PhyloP100		2.1
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
Mutation Taster		=64/36	polymorphism (auto)

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

Other links and lift over

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