rs2304277

chr3-9759396-G-Achr3-9759396-G-C

Variant summary

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

The NM_003656.5(CAMK1):c.912+92C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,578,702 control chromosomes in the GnomAD database, including 45,853 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 0.26 (5764 hom., cov: 32)
  • Exomes 𝑓: 0.23 (40089 hom.)
• Consequence: CAMK1 NM_003656.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391

Genes affected

CAMK1 (HGNC:1459): (calcium/calmodulin dependent protein kinase I) Calcium/calmodulin-dependent protein kinase I is expressed in many tissues and is a component of a calmodulin-dependent protein kinase cascade. Calcium/calmodulin directly activates calcium/calmodulin-dependent protein kinase I by binding to the enzyme and indirectly promotes the phosphorylation and synergistic activation of the enzyme by calcium/calmodulin-dependent protein kinase I kinase. [provided by RefSeq, Jul 2008]

OGG1 (HGNC:8125): (8-oxoguanine DNA glycosylase) This gene encodes the enzyme responsible for the excision of 8-oxoguanine, a mutagenic base byproduct which occurs as a result of exposure to reactive oxygen. The action of this enzyme includes lyase activity for chain cleavage. Alternative splicing of the C-terminal region of this gene classifies splice variants into two major groups, type 1 and type 2, depending on the last exon of the sequence. Type 1 alternative splice variants end with exon 7 and type 2 end with exon 8. All variants share the N-terminal region in common, which contains a mitochondrial targeting signal that is essential for mitochondrial localization. Many alternative splice variants for this gene have been described, but the full-length nature for every variant has not been determined. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK1	NM_003656.5	c.912+92C>T		intron_variant		ENST00000256460.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK1	ENST00000256460.8	c.912+92C>T		intron_variant		1	NM_003656.5	P1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39303 AN: 151962 Hom.: 5748 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.226 AC: 322579 AN: 1426622 Hom.: 40089 Cov.: 25 AF XY: 0.226 AC XY: 161025 AN XY: 711776

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.519

Gnomad4 SAS exome AF: 0.287

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.248

GnomAD4 genome AF: 0.259 AC: 39356 AN: 152080 Hom.: 5764 Cov.: 32 AF XY: 0.257 AC XY: 19105 AN XY: 74366

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.245

Alfa AF: 0.191 Hom.: 1099

Bravo AF: 0.277

Asia WGS AF: 0.388 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.17
Dann	Benign	0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2304277; hg19: chr3-9801080; COSMIC: COSV56538904; COSMIC: COSV56538904;