NM_006888.6:c.273A>G
Variant names:
Variant summary
Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_006888.6(CALM1):c.273A>G(p.Arg91Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Consequence
CALM1
NM_006888.6 synonymous
NM_006888.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.85
Publications
0 publications found
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 syndromeInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- long QT syndrome 14Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P
- catecholaminergic polymorphic ventricular tachycardia 4Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
- catecholaminergic polymorphic ventricular tachycardiaInheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
Variant 14-90403956-A-G is Benign according to our data. Variant chr14-90403956-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 542138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.85 with no splicing effect.
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 | MANE Select | c.273A>G | p.Arg91Arg | synonymous | Exon 4 of 6 | NP_008819.1 | P0DP23 | ||
| CALM1 | c.276A>G | p.Arg92Arg | synonymous | Exon 4 of 6 | NP_001350599.1 | ||||
| CALM1 | c.165A>G | p.Arg55Arg | synonymous | Exon 4 of 6 | NP_001350598.1 | Q96HY3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CALM1 | TSL:1 MANE Select | c.273A>G | p.Arg91Arg | synonymous | Exon 4 of 6 | ENSP00000349467.4 | P0DP23 | ||
| CALM1 | TSL:1 | c.165A>G | p.Arg55Arg | synonymous | Exon 4 of 6 | ENSP00000442853.2 | Q96HY3 | ||
| CALM1 | TSL:1 | n.2403A>G | non_coding_transcript_exon | Exon 3 of 5 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152240
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
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Gnomad EAS
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Gnomad FIN
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GnomAD4 exome Cov.: 26
GnomAD4 exome
Cov.:
26
GnomAD4 genome 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74380 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152240
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74380
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41460
American (AMR)
AF:
AC:
0
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5204
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10628
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68042
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely benign
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
-
-
1
Cardiovascular phenotype (1)
-
-
1
Catecholaminergic polymorphic ventricular tachycardia 4;C4015671:Long QT syndrome 14 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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