rs151118217

Variant names:

• chr5-150222566-C-G
• rs151118217
• NM_015981.4:c.*144G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-150222566-C-G
• chr5-150222566-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015981.4(CAMK2A):​c.*144G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 910,248 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00052 (3 hom.)
• Consequence: CAMK2A NM_015981.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.739
• Publications: 0 publications found

Genes affected

CAMK2A (HGNC:1460): (calcium/calmodulin dependent protein kinase II alpha) The product of this gene belongs to the serine/threonine protein kinases family, and to the Ca(2+)/calmodulin-dependent protein kinases subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. This calcium calmodulin-dependent protein kinase is composed of four different chains: alpha, beta, gamma, and delta. The alpha chain encoded by this gene is required for hippocampal long-term potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)-dependent activity, this protein can undergo autophosphorylation, resulting in CaM-independent activity. Several transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jun 2018]

SLC6A7 (HGNC:11054): (solute carrier family 6 member 7) This gene is a member of the gamma-aminobutyric acid (GABA) neurotransmitter gene family and encodes a high-affinity mammalian brain L-proline transporter protein. This transporter protein differs from other sodium-dependent plasma membrane carriers by its pharmacological specificity, kinetic properties, and ionic requirements. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-150222566-C-G is Benign according to our data. Variant chr5-150222566-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2655915.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00419 (637/152072) while in subpopulation AFR AF = 0.0147 (608/41486). AF 95% confidence interval is 0.0137. There are 1 homozygotes in GnomAd4. There are 284 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015981.4. 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
	CAMK2A	NM_015981.4	MANE Select	c.*144G>C		3_prime_UTR	Exon 19 of 19	NP_057065.2
	CAMK2A	NM_001363989.1		c.*144G>C		3_prime_UTR	Exon 20 of 20	NP_001350918.1	Q9UQM7-2
	CAMK2A	NM_001363990.1		c.*144G>C		3_prime_UTR	Exon 19 of 19	NP_001350919.1	Q7LDD5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2A	ENST00000671881.1	MANE Select	c.*144G>C		3_prime_UTR	Exon 19 of 19	ENSP00000500386.1	Q9UQM7-2
	CAMK2A	ENST00000348628.11	TSL:1	c.*144G>C		3_prime_UTR	Exon 18 of 18	ENSP00000261793.8	Q9UQM7-1
	CAMK2A	ENST00000672396.1		c.1519G>C	p.Glu507Gln	missense	Exon 18 of 18	ENSP00000499987.1	A0A5F9ZH50

Frequencies

GnomAD3 genomes AF: 0.00417 AC: 633 AN: 151954 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000983

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.000930 AC: 160 AN: 172132 AF XY: 0.000692

Gnomad AFR exome AF: 0.0133

Gnomad AMR exome AF: 0.000844

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000682

Gnomad OTH exome AF: 0.000848

GnomAD4 exome AF: 0.000517 AC: 392 AN: 758176 Hom.: 3 Cov.: 10 AF XY: 0.000408 AC XY: 163 AN XY: 399218

African (AFR) AF: 0.0147 AC: 292 AN: 19834

American (AMR) AF: 0.000748 AC: 27 AN: 36120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21238

East Asian (EAS) AF: 0.00 AC: 0 AN: 34564

South Asian (SAS) AF: 0.0000147 AC: 1 AN: 68010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43622

Middle Eastern (MID) AF: 0.00157 AC: 7 AN: 4454

European-Non Finnish (NFE) AF: 0.0000406 AC: 20 AN: 492950

Other (OTH) AF: 0.00120 AC: 45 AN: 37384

GnomAD4 genome AF: 0.00419 AC: 637 AN: 152072 Hom.: 1 Cov.: 32 AF XY: 0.00382 AC XY: 284 AN XY: 74318

African (AFR) AF: 0.0147 AC: 608 AN: 41486

American (AMR) AF: 0.000981 AC: 15 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67964

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00201 Hom.: 0

Bravo AF: 0.00474

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.63
PhyloP100		0.74
Mutation Taster		=100/0	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: rs151118217; hg19: chr5-149602129;