rs758642

Positions:

• chr17-3883613-G-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.557

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 (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMKK1	NM_032294.3	c.463-133C>T		intron_variant		ENST00000348335.7	NP_115670.1
CAMKK1	NM_172206.2	c.544-133C>T		intron_variant			NP_757343.2
CAMKK1	NM_172207.3	c.463-133C>T		intron_variant			NP_757344.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMKK1	ENST00000348335.7	c.463-133C>T		intron_variant		1	NM_032294.3	ENSP00000323118	P1
CAMKK1	ENST00000158166.5	c.463-133C>T		intron_variant		1		ENSP00000158166
CAMKK1	ENST00000381769.6	c.544-133C>T		intron_variant		1		ENSP00000371188
CAMKK1	ENST00000573483.1	n.1171-133C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51699 AN: 151780 Hom.: 9056 Cov.: 32

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

Gnomad4 AFR exome AF: 0.370

Gnomad4 AMR exome AF: 0.302

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.296

Gnomad4 FIN exome AF: 0.299

Gnomad4 NFE exome AF: 0.363

Gnomad4 OTH exome AF: 0.343

GnomAD4 genome AF: 0.341 AC: 51747 AN: 151898 Hom.: 9071 Cov.: 32 AF XY: 0.335 AC XY: 24839 AN XY: 74236

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.345

Alfa AF: 0.348 Hom.: 13410

Bravo AF: 0.343

Asia WGS AF: 0.226 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.61

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

LitVar

Other links and lift over

dbSNP: rs758642; hg19: chr17-3786907; COSMIC: COSV50120904;