rs917791

Variant names:

• chr7-44229186-A-G
• rs917791
• NM_001220.5:c.1339+202T>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.1339+202T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 611,654 control chromosomes in the GnomAD database, including 42,150 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 0.35 (9669 hom., cov: 33)
  • Exomes 𝑓: 0.37 (32481 hom.)
• Consequence: CAMK2B NM_001220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 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.1339+202T>C		intron	N/A	NP_001211.3
	CAMK2B	NM_001293170.2		c.1225+1820T>C		intron	N/A	NP_001280099.1
	CAMK2B	NM_172078.3		c.1225+1820T>C		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.1339+202T>C		intron	N/A	ENSP00000379098.2
	CAMK2B	ENST00000440254.6	TSL:1	c.1225+1820T>C		intron	N/A	ENSP00000397937.2
	CAMK2B	ENST00000395747.6	TSL:1	c.1153+1820T>C		intron	N/A	ENSP00000379096.2

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53570 AN: 151966 Hom.: 9662 Cov.: 33

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.383

GnomAD2 exomes AF: 0.335 AC: 21066 AN: 62836 AF XY: 0.338

Gnomad AFR exome AF: 0.315

Gnomad AMR exome AF: 0.265

Gnomad ASJ exome AF: 0.473

Gnomad EAS exome AF: 0.188

Gnomad FIN exome AF: 0.325

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.369 AC: 169654 AN: 459570 Hom.: 32481 Cov.: 5 AF XY: 0.373 AC XY: 89790 AN XY: 240508

African (AFR) AF: 0.324 AC: 3932 AN: 12142

American (AMR) AF: 0.268 AC: 4934 AN: 18388

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 6374 AN: 13498

East Asian (EAS) AF: 0.215 AC: 6492 AN: 30178

South Asian (SAS) AF: 0.395 AC: 17495 AN: 44304

European-Finnish (FIN) AF: 0.322 AC: 13763 AN: 42780

Middle Eastern (MID) AF: 0.493 AC: 1563 AN: 3172

European-Non Finnish (NFE) AF: 0.392 AC: 105595 AN: 269228

Other (OTH) AF: 0.367 AC: 9506 AN: 25880

GnomAD4 genome AF: 0.352 AC: 53600 AN: 152084 Hom.: 9669 Cov.: 33 AF XY: 0.348 AC XY: 25889 AN XY: 74352

African (AFR) AF: 0.316 AC: 13108 AN: 41492

American (AMR) AF: 0.300 AC: 4592 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1642 AN: 3468

East Asian (EAS) AF: 0.182 AC: 941 AN: 5162

South Asian (SAS) AF: 0.386 AC: 1864 AN: 4824

European-Finnish (FIN) AF: 0.324 AC: 3428 AN: 10590

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26604 AN: 67936

Other (OTH) AF: 0.381 AC: 805 AN: 2114

Alfa AF: 0.362 Hom.: 2963

Bravo AF: 0.346

Asia WGS AF: 0.310 AC: 1081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.42
PhyloP100		0.31
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: rs917791; hg19: chr7-44268785; COSMIC: COSV51659847; COSMIC: COSV51659847;