rs1127065

Positions:

• chr7-44220272-C-G
• chr7-44220272-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001220.5(CAMK2B):​c.1791G>C​(p.Pro597=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,612,832 control chromosomes in the GnomAD database, including 360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P597P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.014 (20 hom., cov: 33)
  • Exomes 𝑓: 0.020 (340 hom.)
• Consequence: CAMK2B NM_001220.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.83

Genes affected

CAMK2B (HGNC:1461): (calcium/calmodulin dependent protein kinase II beta) The product of this gene belongs to the serine/threonine protein kinase family and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. In mammalian cells, the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is a beta chain. It is possible that distinct isoforms of this chain have different cellular localizations and interact differently with calmodulin. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 7-44220272-C-G is Benign according to our data. Variant chr7-44220272-C-G is described in ClinVar as [Benign]. Clinvar id is 1616494.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.83 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0141 (2142/152108) while in subpopulation SAS AF= 0.0253 (122/4820). AF 95% confidence interval is 0.0217. There are 20 homozygotes in gnomad4. There are 1054 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2142 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK2B	NM_001220.5	c.1791G>C	p.Pro597=	synonymous_variant	23/24	ENST00000395749.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK2B	ENST00000395749.7	c.1791G>C	p.Pro597=	synonymous_variant	23/24	1	NM_001220.5

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2141 AN: 151992 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.00413

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0330

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.0170 AC: 4213 AN: 248552 Hom.: 51 AF XY: 0.0177 AC XY: 2391 AN XY: 134856

Gnomad AFR exome AF: 0.00336

Gnomad AMR exome AF: 0.00490

Gnomad ASJ exome AF: 0.0126

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.0256

Gnomad FIN exome AF: 0.0390

Gnomad NFE exome AF: 0.0192

Gnomad OTH exome AF: 0.0160

GnomAD4 exome AF: 0.0199 AC: 29112 AN: 1460724 Hom.: 340 Cov.: 45 AF XY: 0.0202 AC XY: 14702 AN XY: 726648

Gnomad4 AFR exome AF: 0.00311

Gnomad4 AMR exome AF: 0.00561

Gnomad4 ASJ exome AF: 0.0141

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0270

Gnomad4 FIN exome AF: 0.0391

Gnomad4 NFE exome AF: 0.0205

Gnomad4 OTH exome AF: 0.0193

GnomAD4 genome AF: 0.0141 AC: 2142 AN: 152108 Hom.: 20 Cov.: 33 AF XY: 0.0142 AC XY: 1054 AN XY: 74332

Gnomad4 AFR AF: 0.00412

Gnomad4 AMR AF: 0.00431

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0253

Gnomad4 FIN AF: 0.0330

Gnomad4 NFE AF: 0.0198

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00108 Hom.: 17968

EpiCase AF: 0.0183

EpiControl AF: 0.0159

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.8
DANN	Benign	0.82

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: rs1127065; hg19: chr7-44259871;