rs293794

Positions:

• chr3-9761943-A-G

Variant summary

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

The ENST00000256460.8(CAMK1):​c.430-186T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 790,964 control chromosomes in the GnomAD database, including 13,327 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 0.19 (3120 hom., cov: 32)
  • Exomes 𝑓: 0.17 (10207 hom.)
• Consequence: CAMK1 ENST00000256460.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMK1	NM_003656.5	c.430-186T>C		intron_variant		ENST00000256460.8	NP_003647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMK1	ENST00000256460.8	c.430-186T>C		intron_variant		1	NM_003656.5	ENSP00000256460	P1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29337 AN: 152030 Hom.: 3118 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.0462

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.171 AC: 109241 AN: 638816 Hom.: 10207 Cov.: 9 AF XY: 0.169 AC XY: 55123 AN XY: 326948

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.0886

Gnomad4 EAS exome AF: 0.0532

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.193 AC: 29345 AN: 152148 Hom.: 3120 Cov.: 32 AF XY: 0.191 AC XY: 14224 AN XY: 74390

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.0937

Gnomad4 EAS AF: 0.0461

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.165

Alfa AF: 0.174 Hom.: 2399

Bravo AF: 0.187

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.29
DANN	Benign	0.46

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: rs293794; hg19: chr3-9803627;