rs77158048

Variant names:

• chr7-44220086-G-A
• rs77158048
• NM_001220.5:c.1977C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-44220086-G-A
• chr7-44220086-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001220.5(CAMK2B):​c.1977C>T​(p.Gly659Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,601,746 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (57 hom., cov: 34)
  • Exomes 𝑓: 0.0016 (53 hom.)
• Consequence: CAMK2B NM_001220.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -4.75
• Publications: 1 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 7-44220086-G-A is Benign according to our data. Variant chr7-44220086-G-A is described in ClinVar as Benign. ClinVar VariationId is 783493.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.75 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0134 (2046/152304) while in subpopulation AFR AF = 0.0455 (1892/41560). AF 95% confidence interval is 0.0438. There are 57 homozygotes in GnomAd4. There are 943 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2046 AD gene.

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.1977C>T	p.Gly659Gly	synonymous	Exon 23 of 24	NP_001211.3
	CAMK2B	NM_001293170.2		c.1605C>T	p.Gly535Gly	synonymous	Exon 20 of 21	NP_001280099.1	Q13554-2
	CAMK2B	NM_172078.3		c.1605C>T	p.Gly535Gly	synonymous	Exon 20 of 21	NP_742075.1	Q13554-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2B	ENST00000395749.7	TSL:1 MANE Select	c.1977C>T	p.Gly659Gly	synonymous	Exon 23 of 24	ENSP00000379098.2	Q13554-1
	CAMK2B	ENST00000440254.6	TSL:1	c.1605C>T	p.Gly535Gly	synonymous	Exon 20 of 21	ENSP00000397937.2	Q13554-2
	CAMK2B	ENST00000395747.6	TSL:1	c.1533C>T	p.Gly511Gly	synonymous	Exon 19 of 19	ENSP00000379096.2	Q13554-5

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2042 AN: 152186 Hom.: 56 Cov.: 34

Gnomad AFR AF: 0.0456

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00641

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00372 AC: 856 AN: 230216 AF XY: 0.00274

Gnomad AFR exome AF: 0.0467

Gnomad AMR exome AF: 0.00237

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000242

Gnomad OTH exome AF: 0.00297

GnomAD4 exome AF: 0.00156 AC: 2255 AN: 1449442 Hom.: 53 Cov.: 32 AF XY: 0.00141 AC XY: 1019 AN XY: 720754

African (AFR) AF: 0.0468 AC: 1558 AN: 33286

American (AMR) AF: 0.00265 AC: 116 AN: 43768

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 25948

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39264

South Asian (SAS) AF: 0.00202 AC: 172 AN: 85224

European-Finnish (FIN) AF: 0.0000210 AC: 1 AN: 47580

Middle Eastern (MID) AF: 0.00261 AC: 15 AN: 5754

European-Non Finnish (NFE) AF: 0.000153 AC: 170 AN: 1108586

Other (OTH) AF: 0.00368 AC: 221 AN: 60032

GnomAD4 genome AF: 0.0134 AC: 2046 AN: 152304 Hom.: 57 Cov.: 34 AF XY: 0.0127 AC XY: 943 AN XY: 74458

African (AFR) AF: 0.0455 AC: 1892 AN: 41560

American (AMR) AF: 0.00640 AC: 98 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68028

Other (OTH) AF: 0.00992 AC: 21 AN: 2116

Alfa AF: 0.00747 Hom.: 9

Bravo AF: 0.0156

Asia WGS AF: 0.00202 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	CAMK2B-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.7
DANN	Benign	0.91
PhyloP100		-4.8
Mutation Taster		=82/18	polymorphism

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: rs77158048; hg19: chr7-44259685; COSMIC: COSV51662860;