dbSNP rs11671131: CALM3:c.4-599T>C (chr19-46605228-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005184.4(CALM3):c.4-599T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,800 control chromosomes in the GnomAD database, including 2,668 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 0.18 ( 2652 hom., cov: 33)

Exomes 𝑓: 0.16 ( 16 hom. )

Consequence

CALM3
NM_005184.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.948

Publications

1 publications found

Variant links:

Genes affected

CALM3 (HGNC:1449): (calmodulin 3) This gene encodes a member of a family of proteins that binds calcium and functions as a enzymatic co-factor. Activity of this protein is important in the regulation of the cell cycle and cytokinesis. Multiple alternatively spliced transcript variants have been observed at this gene. [provided by RefSeq, Aug 2016]

CALM3 Gene-Disease associations (from GenCC):

familial long QT syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
long QT syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
long QT syndrome 16
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
catecholaminergic polymorphic ventricular tachycardia
Inheritance: AD Classification: MODERATE Submitted by: ClinGen, G2P

CALM3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALM3	NM_005184.4 link	c.4-599T>C		intron_variant	Intron 1 of 5	ENST00000291295.14	NP_005175.2	P0DP23P0DP24P0DP25B4DJ51Q9BRL5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALM3	ENST00000291295.14 link	c.4-599T>C		intron_variant	Intron 1 of 5	1	NM_005184.4	ENSP00000291295.8		P0DP25

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27302

AN:

152118

Hom.:

2656

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.318

Gnomad SAS

AF:

0.351

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.166

GnomAD4 exome

AF:

0.163

AC:

AN:

564

Hom.:

Cov.:

AF XY:

0.179

AC XY:

AN XY:

296

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.0385

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.667

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.140

AC:

AN:

442

Other (OTH)

AF:

0.111

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.179

AC:

27302

AN:

152236

Hom.:

2652

Cov.:

AF XY:

0.186

AC XY:

13810

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.201

AC:

8334

AN:

41546

American (AMR)

AF:

0.108

AC:

1651

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

694

AN:

3472

East Asian (EAS)

AF:

0.318

AC:

1643

AN:

5164

South Asian (SAS)

AF:

0.350

AC:

1692

AN:

4830

European-Finnish (FIN)

AF:

0.207

AC:

2191

AN:

10594

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.156

AC:

10631

AN:

68016

Other (OTH)

AF:

0.165

AC:

349

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1147

2295

3442

4590

5737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

312

624

936

1248

1560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.168

Hom.:

1577

Bravo

AF:

0.169

Asia WGS

AF:

0.327

AC:

1136

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.95

(source)

DANN

Benign

0.45

PhyloP100

-0.95

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over