7-44229186-A-G

Position:

• chr7-44229186-A-G

Variant summary

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

The NM_001220.5(CAMK2B):​c.1339+202T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 611,654 control chromosomes in the GnomAD database, including 42,150 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 0.35 (9669 hom., cov: 33)
  • Exomes 𝑓: 0.37 (32481 hom.)
• Consequence: CAMK2B NM_001220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK2B	NM_001220.5	c.1339+202T>C		intron_variant		ENST00000395749.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK2B	ENST00000395749.7	c.1339+202T>C		intron_variant		1	NM_001220.5

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53570 AN: 151966 Hom.: 9662 Cov.: 33

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.383

GnomAD3 exomes AF: 0.335 AC: 21066 AN: 62836 Hom.: 3762 AF XY: 0.338 AC XY: 10660 AN XY: 31558

Gnomad AFR exome AF: 0.315

Gnomad AMR exome AF: 0.265

Gnomad ASJ exome AF: 0.473

Gnomad EAS exome AF: 0.188

Gnomad SAS exome AF: 0.414

Gnomad FIN exome AF: 0.325

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.369 AC: 169654 AN: 459570 Hom.: 32481 Cov.: 5 AF XY: 0.373 AC XY: 89790 AN XY: 240508

Gnomad4 AFR exome AF: 0.324

Gnomad4 AMR exome AF: 0.268

Gnomad4 ASJ exome AF: 0.472

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.395

Gnomad4 FIN exome AF: 0.322

Gnomad4 NFE exome AF: 0.392

Gnomad4 OTH exome AF: 0.367

GnomAD4 genome AF: 0.352 AC: 53600 AN: 152084 Hom.: 9669 Cov.: 33 AF XY: 0.348 AC XY: 25889 AN XY: 74352

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.381

Alfa AF: 0.363 Hom.: 2669

Bravo AF: 0.346

Asia WGS AF: 0.310 AC: 1081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.42

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: rs917791; hg19: chr7-44268785; COSMIC: COSV51659847; COSMIC: COSV51659847;