chr3-49860567-A-G

Variant names:

• chr3-49860567-A-G
• rs2777888
• NM_024046.5:c.776-18T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024046.5(CAMKV):​c.776-18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,610,700 control chromosomes in the GnomAD database, including 185,740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19498 hom., cov: 32)
  • Exomes 𝑓: 0.47 (166242 hom.)
• Consequence: CAMKV NM_024046.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0350

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-49860567-A-G is Benign according to our data. Variant chr3-49860567-A-G is described in ClinVar as [Benign]. Clinvar id is 1269547.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	c.776-18T>C		intron_variant	Intron 8 of 10	ENST00000477224.6	NP_076951.2
CAMKV	NM_001320147.2	c.776-18T>C		intron_variant	Intron 8 of 11		NP_001307076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMKV	ENST00000477224.6	c.776-18T>C		intron_variant	Intron 8 of 10	1	NM_024046.5	ENSP00000419195.1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74501 AN: 151836 Hom.: 19474 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.343

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: 0.488

GnomAD2 exomes AF: 0.399 AC: 97802 AN: 245284 AF XY: 0.396

Gnomad AFR exome AF: 0.643

Gnomad AMR exome AF: 0.286

Gnomad ASJ exome AF: 0.343

Gnomad EAS exome AF: 0.149

Gnomad FIN exome AF: 0.387

Gnomad NFE exome AF: 0.490

Gnomad OTH exome AF: 0.432

GnomAD4 exome AF: 0.467 AC: 681716 AN: 1458746 Hom.: 166242 Cov.: 41 AF XY: 0.461 AC XY: 334512 AN XY: 725406

African (AFR) AF: 0.637 AC: 21278 AN: 33404

American (AMR) AF: 0.299 AC: 13220 AN: 44170

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 9093 AN: 26074

East Asian (EAS) AF: 0.154 AC: 6110 AN: 39650

South Asian (SAS) AF: 0.242 AC: 20780 AN: 85932

European-Finnish (FIN) AF: 0.387 AC: 20614 AN: 53264

Middle Eastern (MID) AF: 0.423 AC: 2436 AN: 5762

European-Non Finnish (NFE) AF: 0.505 AC: 560804 AN: 1110206

Other (OTH) AF: 0.454 AC: 27381 AN: 60284

GnomAD4 genome AF: 0.491 AC: 74573 AN: 151954 Hom.: 19498 Cov.: 32 AF XY: 0.477 AC XY: 35455 AN XY: 74270

African (AFR) AF: 0.634 AC: 26273 AN: 41434

American (AMR) AF: 0.393 AC: 6007 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1188 AN: 3464

East Asian (EAS) AF: 0.143 AC: 740 AN: 5158

South Asian (SAS) AF: 0.234 AC: 1130 AN: 4822

European-Finnish (FIN) AF: 0.382 AC: 4033 AN: 10558

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33543 AN: 67922

Other (OTH) AF: 0.491 AC: 1039 AN: 2116

Alfa AF: 0.477 Hom.: 15471

Bravo AF: 0.505

Asia WGS AF: 0.282 AC: 981 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.85
CADD	Benign	9.4
DANN	Benign	0.65
PhyloP100		0.035
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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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Other links and lift over

dbSNP: rs2777888; hg19: chr3-49898000; COSMIC: COSV56557353; COSMIC: COSV56557353;