chr7-44237052-T-C

Variant names:

• chr7-44237052-T-C
• rs3757837
• NM_001220.5:c.1022-2376A>G

Variant summary

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

The NM_001220.5(CAMK2B):​c.1022-2376A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,256 control chromosomes in the GnomAD database, including 1,813 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 0.15 (1813 hom., cov: 33)
• Consequence: CAMK2B NM_001220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985
• Publications: 17 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2B	NM_001220.5	c.1022-2376A>G		intron_variant	Intron 13 of 23	ENST00000395749.7	NP_001211.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2B	ENST00000395749.7	c.1022-2376A>G		intron_variant	Intron 13 of 23	1	NM_001220.5	ENSP00000379098.2

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22815 AN: 152138 Hom.: 1813 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.150 AC: 22834 AN: 152256 Hom.: 1813 Cov.: 33 AF XY: 0.148 AC XY: 11035 AN XY: 74446

African (AFR) AF: 0.178 AC: 7374 AN: 41530

American (AMR) AF: 0.112 AC: 1721 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 501 AN: 3472

East Asian (EAS) AF: 0.207 AC: 1070 AN: 5176

South Asian (SAS) AF: 0.239 AC: 1151 AN: 4820

European-Finnish (FIN) AF: 0.0930 AC: 988 AN: 10620

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9376 AN: 68016

Other (OTH) AF: 0.159 AC: 337 AN: 2114

Alfa AF: 0.148 Hom.: 2723

Bravo AF: 0.152

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.32
PhyloP100		-0.98
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: rs3757837; hg19: chr7-44276651;