chr7-44249066-G-A

Variant names:

• chr7-44249066-G-A
• rs10441113
• NM_001220.5:c.342-1874C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001220.5(CAMK2B):​c.342-1874C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,054 control chromosomes in the GnomAD database, including 7,996 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 0.31 (7996 hom., cov: 32)
• Consequence: CAMK2B NM_001220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2B	NM_001220.5	MANE Select	c.342-1874C>T		intron	N/A	NP_001211.3
	CAMK2B	NM_001293170.2		c.342-1874C>T		intron	N/A	NP_001280099.1
	CAMK2B	NM_172078.3		c.342-1874C>T		intron	N/A	NP_742075.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2B	ENST00000395749.7	TSL:1 MANE Select	c.342-1874C>T		intron	N/A	ENSP00000379098.2
	CAMK2B	ENST00000440254.6	TSL:1	c.342-1874C>T		intron	N/A	ENSP00000397937.2
	CAMK2B	ENST00000395747.6	TSL:1	c.342-1874C>T		intron	N/A	ENSP00000379096.2

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46524 AN: 151936 Hom.: 8002 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.306 AC: 46525 AN: 152054 Hom.: 7996 Cov.: 32 AF XY: 0.305 AC XY: 22663 AN XY: 74314

African (AFR) AF: 0.166 AC: 6893 AN: 41484

American (AMR) AF: 0.264 AC: 4026 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1453 AN: 3470

East Asian (EAS) AF: 0.106 AC: 547 AN: 5166

South Asian (SAS) AF: 0.284 AC: 1367 AN: 4808

European-Finnish (FIN) AF: 0.430 AC: 4550 AN: 10580

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26518 AN: 67958

Other (OTH) AF: 0.335 AC: 707 AN: 2112

Alfa AF: 0.366 Hom.: 17832

Bravo AF: 0.287

Asia WGS AF: 0.180 AC: 627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.49
DANN	Benign	0.61
PhyloP100		-0.35
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: rs10441113; hg19: chr7-44288665;