rs4834348

Positions:

• chr4-113505159-G-T

Variant summary

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

The NM_001321571.2(CAMK2D):​c.985-124C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 473,122 control chromosomes in the GnomAD database, including 46,515 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 0.43 (14771 hom., cov: 30)
  • Exomes 𝑓: 0.43 (31744 hom.)
• Consequence: CAMK2D NM_001321571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66

Genes affected

CAMK2D (HGNC:1462): (calcium/calmodulin dependent protein kinase II delta) 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 delta chain. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Distinct isoforms of this chain have different expression patterns.[provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMK2D	NM_001321571.2	c.985-124C>A		intron_variant		ENST00000511664.6	NP_001308500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMK2D	ENST00000511664.6	c.985-124C>A		intron_variant		2	NM_001321571.2	ENSP00000425824

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65693 AN: 151774 Hom.: 14769 Cov.: 30

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.430 AC: 138125 AN: 321230 Hom.: 31744 AF XY: 0.432 AC XY: 73522 AN XY: 169994

Gnomad4 AFR exome AF: 0.463

Gnomad4 AMR exome AF: 0.323

Gnomad4 ASJ exome AF: 0.483

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.398

Gnomad4 FIN exome AF: 0.363

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.442

GnomAD4 genome AF: 0.433 AC: 65718 AN: 151892 Hom.: 14771 Cov.: 30 AF XY: 0.421 AC XY: 31241 AN XY: 74258

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.459

Alfa AF: 0.461 Hom.: 7659

Bravo AF: 0.436

Asia WGS AF: 0.248 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.71

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: rs4834348; hg19: chr4-114426315; COSMIC: COSV56432167;