chr4-113514721-T-C

Position:

• chr4-113514721-T-C

Variant summary

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

The NM_001321571.2(CAMK2D):​c.819+348A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,236 control chromosomes in the GnomAD database, including 1,292 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 0.11 (1292 hom., cov: 32)
• Consequence: CAMK2D NM_001321571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK2D	NM_001321571.2	c.819+348A>G		intron_variant		ENST00000511664.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK2D	ENST00000511664.6	c.819+348A>G		intron_variant		2	NM_001321571.2

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17020 AN: 152116 Hom.: 1290 Cov.: 32

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0734

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.112 AC: 17021 AN: 152236 Hom.: 1292 Cov.: 32 AF XY: 0.115 AC XY: 8584 AN XY: 74408

Gnomad4 AFR AF: 0.0245

Gnomad4 AMR AF: 0.0733

Gnomad4 ASJ AF: 0.0983

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.117

Alfa AF: 0.132 Hom.: 1457

Bravo AF: 0.0972

Asia WGS AF: 0.152 AC: 526 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.53

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: rs3815072; hg19: chr4-114435877;