chr4-113440730-G-A

Position:

• chr4-113440730-G-A

Variant summary

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

The ENST00000683023.1(CAMK2D):​c.*29+14996C>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.078 in 152,160 control chromosomes in the GnomAD database, including 501 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 0.078 (501 hom., cov: 31)
• Consequence: CAMK2D ENST00000683023.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07

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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK2D	ENST00000683023.1	c.*29+14996C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0780 AC: 11858 AN: 152042 Hom.: 501 Cov.: 31

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0649

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.0857

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.0718

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.0804

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

GnomAD4 genome AF: 0.0780 AC: 11864 AN: 152160 Hom.: 501 Cov.: 31 AF XY: 0.0768 AC XY: 5712 AN XY: 74390

Gnomad4 AFR AF: 0.0667

Gnomad4 AMR AF: 0.0648

Gnomad4 ASJ AF: 0.0844

Gnomad4 EAS AF: 0.0859

Gnomad4 SAS AF: 0.0687

Gnomad4 FIN AF: 0.0718

Gnomad4 NFE AF: 0.0884

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0857 Hom.: 298

Bravo AF: 0.0776

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.3
DANN	Benign	0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7684418; hg19: chr4-114361886;