rs293795

chr3-9757429-A-G

Variant summary

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

The NM_003656.5(CAMK1):c.*110T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,607,078 control chromosomes in the GnomAD database, including 28,121 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 0.21 (3953 hom., cov: 32)
  • Exomes 𝑓: 0.18 (24168 hom.)
• Consequence: CAMK1 NM_003656.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK1	NM_003656.5	c.*110T>C		3_prime_UTR_variant	12/12	ENST00000256460.8
OGG1	NM_002542.6			downstream_gene_variant		ENST00000344629.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK1	ENST00000256460.8	c.*110T>C		3_prime_UTR_variant	12/12	1	NM_003656.5	P1
OGG1	ENST00000344629.12			downstream_gene_variant		1	NM_002542.6	P1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32475 AN: 152058 Hom.: 3952 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0433

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.177 AC: 258093 AN: 1454902 Hom.: 24168 Cov.: 35 AF XY: 0.176 AC XY: 127361 AN XY: 723038

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.0980

Gnomad4 EAS exome AF: 0.0485

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.239

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.213 AC: 32483 AN: 152176 Hom.: 3953 Cov.: 32 AF XY: 0.212 AC XY: 15790 AN XY: 74426

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0432

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.190

Alfa AF: 0.180 Hom.: 2944

Bravo AF: 0.210

Asia WGS AF: 0.0940 AC: 325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.4
Dann	Benign	0.76

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: rs293795; hg19: chr3-9799113; COSMIC: COSV56540400; COSMIC: COSV56540400;