3-9767398-T-C

Variant names:

• chr3-9767398-T-C
• rs293796
• NM_003656.5:c.83+269A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003656.5(CAMK1):​c.83+269A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 152,304 control chromosomes in the GnomAD database, including 65,920 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 0.93 (65920 hom., cov: 33)
• Consequence: CAMK1 NM_003656.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003656.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK1	NM_003656.5	MANE Select	c.83+269A>G		intron	N/A	NP_003647.1
	OGG1	NM_001434448.1		c.948+10582T>C		intron	N/A	NP_001421377.1
	OGG1	NM_001434445.1		c.948+10582T>C		intron	N/A	NP_001421374.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK1	ENST00000256460.8	TSL:1 MANE Select	c.83+269A>G		intron	N/A	ENSP00000256460.3
	OGG1	ENST00000426518.5	TSL:5	c.293-14115T>C		intron	N/A	ENSP00000399810.1
	CAMK1	ENST00000411972.1	TSL:3	c.83+269A>G		intron	N/A	ENSP00000404587.1

Frequencies

GnomAD3 genomes AF: 0.929 AC: 141389 AN: 152186 Hom.: 65864 Cov.: 33

Gnomad AFR AF: 0.983

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.918

Gnomad OTH AF: 0.915

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.929 AC: 141503 AN: 152304 Hom.: 65920 Cov.: 33 AF XY: 0.927 AC XY: 69055 AN XY: 74472

African (AFR) AF: 0.984 AC: 40886 AN: 41570

American (AMR) AF: 0.918 AC: 14049 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3173 AN: 3470

East Asian (EAS) AF: 0.762 AC: 3948 AN: 5178

South Asian (SAS) AF: 0.819 AC: 3948 AN: 4822

European-Finnish (FIN) AF: 0.938 AC: 9945 AN: 10608

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.918 AC: 62433 AN: 68032

Other (OTH) AF: 0.916 AC: 1938 AN: 2116

Alfa AF: 0.919 Hom.: 120472

Bravo AF: 0.932

Asia WGS AF: 0.805 AC: 2798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.88
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs293796; hg19: chr3-9809082;