Genetic Variant CALM1:c.-161C>A (chr14-90397070-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006888.6(CALM1):c.-161C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000185 in 540,516 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

CALM1
NM_006888.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.253

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006888.6. 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_006888.6	MANE Select	c.-161C>A		5_prime_UTR	Exon 1 of 6	NP_008819.1	P0DP23
	CALM1	NM_001363669.2		c.-106+412C>A		intron	N/A	NP_001350598.1	Q96HY3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CALM1	ENST00000356978.9	TSL:1 MANE Select	c.-161C>A	5_prime_UTR	Exon 1 of 6	ENSP00000349467.4	P0DP23
CALM1	ENST00000971957.1		c.-161C>A	5_prime_UTR	Exon 1 of 6	ENSP00000642016.1
CALM1	ENST00000447653.8	TSL:2	c.-366C>A	5_prime_UTR	Exon 1 of 7	ENSP00000403491.4	Q96HY3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000185

AC:

AN:

540516

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

288188

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13968

American (AMR)

AF:

0.0000416

AC:

AN:

24064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15884

East Asian (EAS)

AF:

0.00

AC:

AN:

31704

South Asian (SAS)

AF:

0.00

AC:

AN:

52738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34100

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2664

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

335948

Other (OTH)

AF:

0.00

AC:

AN:

29446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

6.4

(source)

DANN

Benign

0.85

PhyloP100

-0.25

PromoterAI

-0.015

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over