Genetic Variant CAMKV:p.Asn217Asn (chr3-49860840-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024046.5(CAMKV):c.651T>C(p.Asn217Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,613,624 control chromosomes in the GnomAD database, including 186,207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19521 hom., cov: 31)

Exomes 𝑓: 0.47 ( 166686 hom. )

Consequence

CAMKV
NM_024046.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.86

Variant links:

Genes affected

CAMKV (HGNC:28788): (CaM kinase like vesicle associated) Predicted to enable calmodulin binding activity and calmodulin-dependent protein kinase activity. Predicted to be involved in peptidyl-serine phosphorylation. Predicted to be located in cytoplasmic vesicle membrane and plasma membrane. Predicted to be active in glutamatergic synapse and postsynapse. [provided by Alliance of Genome Resources, Apr 2022]

CAMKV links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 3-49860840-A-G is Benign according to our data. Variant chr3-49860840-A-G is described in ClinVar as [Benign]. Clinvar id is 1297960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMKV	NM_024046.5 link	c.651T>C	p.Asn217Asn	synonymous_variant	Exon 8 of 11	ENST00000477224.6	NP_076951.2	Q8NCB2-1A0A140VKD5
CAMKV	NM_001320147.2 link	c.651T>C	p.Asn217Asn	synonymous_variant	Exon 8 of 12		NP_001307076.1	Q8NCB2-3A0A024R331

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMKV	ENST00000477224.6 link	c.651T>C	p.Asn217Asn	synonymous_variant	Exon 8 of 11	1	NM_024046.5	ENSP00000419195.1		Q8NCB2-1

Frequencies

GnomAD3 genomes

AF:

0.491

AC:

74522

AN:

151856

Hom.:

19497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.634

Gnomad AMI

AF:

0.536

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.494

Gnomad OTH

AF:

0.489

GnomAD2 exomes

AF:

0.399

AC:

100383

AN:

251356

AF XY:

0.397

show subpopulations

Gnomad AFR exome

AF:

0.644

Gnomad AMR exome

AF:

0.286

Gnomad ASJ exome

AF:

0.343

Gnomad EAS exome

AF:

0.149

Gnomad FIN exome

AF:

0.386

Gnomad NFE exome

AF:

0.490

Gnomad OTH exome

AF:

0.433

GnomAD4 exome

AF:

0.467

AC:

682994

AN:

1461650

Hom.:

166686

Cov.:

AF XY:

0.461

AC XY:

335292

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.637

AC:

21328

AN:

33478

American (AMR)

AF:

0.299

AC:

13391

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

9118

AN:

26132

East Asian (EAS)

AF:

0.154

AC:

6118

AN:

39700

South Asian (SAS)

AF:

0.242

AC:

20884

AN:

86256

European-Finnish (FIN)

AF:

0.387

AC:

20657

AN:

53376

Middle Eastern (MID)

AF:

0.423

AC:

2438

AN:

5768

European-Non Finnish (NFE)

AF:

0.505

AC:

561621

AN:

1111824

Other (OTH)

AF:

0.454

AC:

27439

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

20306

40612

60917

81223

101529

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.491

AC:

74594

AN:

151974

Hom.:

19521

Cov.:

AF XY:

0.477

AC XY:

35465

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.634

AC:

26286

AN:

41434

American (AMR)

AF:

0.393

AC:

6006

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

1187

AN:

3470

East Asian (EAS)

AF:

0.144

AC:

742

AN:

5166

South Asian (SAS)

AF:

0.234

AC:

1129

AN:

4818

European-Finnish (FIN)

AF:

0.382

AC:

4037

AN:

10556

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.494

AC:

33548

AN:

67930

Other (OTH)

AF:

0.492

AC:

1039

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1817

3634

5450

7267

9084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.488

Hom.:

36701

Bravo

AF:

0.505

Asia WGS

AF:

0.283

AC:

984

AN:

3478

EpiCase

AF:

0.491

EpiControl

AF:

0.491

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 25, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.3

(source)

DANN

Benign

0.81

PhyloP100

1.9

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

Publications

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3-49860840-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over