dbSNP rs115788075: CALM1:c.-106+183C>T (chr14-90396841-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_001363669.2(CALM1):c.-106+183C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 177,276 control chromosomes in the GnomAD database, including 204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.034 ( 197 hom., cov: 32)

Exomes 𝑓: 0.012 ( 7 hom. )

Consequence

CALM1
NM_001363669.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.197

Publications

0 publications found

Variant links:

Genes affected

CALM1 (HGNC:1442): (calmodulin 1) This gene encodes one of three calmodulin proteins which are members of the EF-hand calcium-binding protein family. Calcium-induced activation of calmodulin regulates and modulates the function of cardiac ion channels. Two pseudogenes have been identified on chromosome 7 and X. Multiple transcript variants encoding different isoforms have been found for this gene.A missense mutation in the CALM1 gene has been associated with ventricular tachycardia.[provided by RefSeq, May 2020]

CALM1 Gene-Disease associations (from GenCC):

long QT syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
long QT syndrome 14
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P
catecholaminergic polymorphic ventricular tachycardia 4
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
catecholaminergic polymorphic ventricular tachycardia
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet

CALM1 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=-0.44).

BP6

Variant 14-90396841-C-T is Benign according to our data. Variant chr14-90396841-C-T is described in ClinVar as Benign. ClinVar VariationId is 670029.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0962 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363669.2. 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
	CALM1	NM_001363669.2		c.-106+183C>T		intron	N/A	NP_001350598.1	Q96HY3
	CALM1	NM_006888.6	MANE Select	c.-390C>T		upstream_gene	N/A	NP_008819.1	P0DP23

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CALM1	ENST00000557020.5	TSL:4	c.-106+183C>T	intron	N/A	ENSP00000451062.1	G3V361
CALM1	ENST00000356978.9	TSL:1 MANE Select	c.-390C>T	upstream_gene	N/A	ENSP00000349467.4	P0DP23
CALM1	ENST00000971957.1		c.-390C>T	upstream_gene	N/A	ENSP00000642016.1

Frequencies

GnomAD3 genomes

AF:

0.0338

AC:

5145

AN:

152126

Hom.:

199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0990

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0188

Gnomad ASJ

AF:

0.0276

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.0287

Gnomad NFE

AF:

0.00687

Gnomad OTH

AF:

0.0325

GnomAD4 exome

AF:

0.0118

AC:

296

AN:

25038

Hom.:

AF XY:

0.0116

AC XY:

153

AN XY:

13170

show subpopulations

African (AFR)

AF:

0.0986

AC:

AN:

862

American (AMR)

AF:

0.0123

AC:

AN:

648

Ashkenazi Jewish (ASJ)

AF:

0.0262

AC:

AN:

916

East Asian (EAS)

AF:

0.00

AC:

AN:

1308

South Asian (SAS)

AF:

0.0147

AC:

AN:

272

European-Finnish (FIN)

AF:

0.00498

AC:

AN:

2208

Middle Eastern (MID)

AF:

0.0328

AC:

AN:

122

European-Non Finnish (NFE)

AF:

0.00744

AC:

126

AN:

16932

Other (OTH)

AF:

0.0192

AC:

AN:

1770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.0338

AC:

5145

AN:

152238

Hom.:

197

Cov.:

AF XY:

0.0324

AC XY:

2409

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0987

AC:

4102

AN:

41552

American (AMR)

AF:

0.0188

AC:

287

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0276

AC:

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5172

South Asian (SAS)

AF:

0.0139

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00358

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.0308

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00687

AC:

467

AN:

67994

Other (OTH)

AF:

0.0322

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

240

480

721

961

1201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0271

Hom.:

Bravo

AF:

0.0381

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.9

(source)

DANN

Benign

0.68

PhyloP100

0.20

PromoterAI

-0.0046

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over