rs2304277

Variant names:

• chr3-9759396-G-A
• rs2304277
• NM_003656.5:c.912+92C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-9759396-G-A
• chr3-9759396-G-C

Variant summary

Our verdict is Benign. The variant received -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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 27 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK1	NM_003656.5	MANE Select	c.912+92C>T		intron	N/A	NP_003647.1	B0YIY3
	OGG1	NM_016821.3		c.948+2580G>A		intron	N/A	NP_058214.1	O15527-4
	OGG1	NM_016826.3		c.747+4511G>A		intron	N/A	NP_058434.1	E5KPM6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK1	ENST00000256460.8	TSL:1 MANE Select	c.912+92C>T		intron	N/A	ENSP00000256460.3	Q14012
	OGG1	ENST00000302036.12	TSL:1	c.948+2580G>A		intron	N/A	ENSP00000306561.7	O15527-4
	OGG1	ENST00000352937.6	TSL:1	c.747+4511G>A		intron	N/A	ENSP00000344899.6	H7BXZ1

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

African (AFR) AF: 0.357 AC: 11682 AN: 32714

American (AMR) AF: 0.352 AC: 15720 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 5112 AN: 25916

East Asian (EAS) AF: 0.519 AC: 20495 AN: 39522

South Asian (SAS) AF: 0.287 AC: 24508 AN: 85478

European-Finnish (FIN) AF: 0.143 AC: 7649 AN: 53372

Middle Eastern (MID) AF: 0.326 AC: 1855 AN: 5698

European-Non Finnish (NFE) AF: 0.205 AC: 220883 AN: 1080024

Other (OTH) AF: 0.248 AC: 14675 AN: 59262

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

African (AFR) AF: 0.350 AC: 14496 AN: 41452

American (AMR) AF: 0.264 AC: 4038 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 650 AN: 3468

East Asian (EAS) AF: 0.555 AC: 2854 AN: 5146

South Asian (SAS) AF: 0.300 AC: 1445 AN: 4822

European-Finnish (FIN) AF: 0.148 AC: 1569 AN: 10594

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13528 AN: 67994

Other (OTH) AF: 0.245 AC: 518 AN: 2112

Alfa AF: 0.204 Hom.: 2364

Bravo AF: 0.277

Asia WGS AF: 0.388 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.17
DANN	Benign	0.18
PhyloP100		-0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2304277; hg19: chr3-9801080; COSMIC: COSV56538904; COSMIC: COSV56538904;