7-44235043-T-G

Variant summary

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

The NM_001220.5(CAMK2B):c.1022-367A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,110 control chromosomes in the GnomAD database, including 10,445 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 0.36 (10445 hom., cov: 34)
• Consequence: CAMK2B NM_001220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK2B	NM_001220.5	c.1022-367A>C		intron_variant		ENST00000395749.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK2B	ENST00000395749.7	c.1022-367A>C		intron_variant		1	NM_001220.5

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54516 AN: 151994 Hom.: 10449 Cov.: 34

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.358 AC: 54531 AN: 152110 Hom.: 10445 Cov.: 34 AF XY: 0.355 AC XY: 26360 AN XY: 74358

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.410

Alfa AF: 0.248 Hom.: 607

Bravo AF: 0.349

Asia WGS AF: 0.335 AC: 1168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.24
Dann	Benign	0.68

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: rs2075076; hg19: chr7-44274642;