NM_001220.5:c.1022-367A>C

Variant names:

• chr7-44235043-T-G
• rs2075076
• NM_001220.5:c.1022-367A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

CAMK2B Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 40

  Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina
• intellectual disability, autosomal dominant 54

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001220.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2B	NM_001220.5	MANE Select	c.1022-367A>C		intron	N/A	NP_001211.3
	CAMK2B	NM_001293170.2		c.1022-367A>C		intron	N/A	NP_001280099.1
	CAMK2B	NM_172078.3		c.1022-367A>C		intron	N/A	NP_742075.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2B	ENST00000395749.7	TSL:1 MANE Select	c.1022-367A>C		intron	N/A	ENSP00000379098.2
	CAMK2B	ENST00000440254.6	TSL:1	c.1022-367A>C		intron	N/A	ENSP00000397937.2
	CAMK2B	ENST00000395747.6	TSL:1	c.947-364A>C		intron	N/A	ENSP00000379096.2

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

African (AFR) AF: 0.233 AC: 9692 AN: 41538

American (AMR) AF: 0.321 AC: 4911 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1728 AN: 3466

East Asian (EAS) AF: 0.257 AC: 1330 AN: 5166

South Asian (SAS) AF: 0.432 AC: 2084 AN: 4828

European-Finnish (FIN) AF: 0.358 AC: 3785 AN: 10568

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29456 AN: 67936

Other (OTH) AF: 0.410 AC: 866 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.24
DANN	Benign	0.68
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2075076; hg19: chr7-44274642;