14-90404693-C-T
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2
The NM_006888.6(CALM1):c.426C>T(p.Phe142=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000112 in 1,609,556 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000010 ( 1 hom. )
Consequence
CALM1
NM_006888.6 synonymous
NM_006888.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.72
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 14-90404693-C-T is Benign according to our data. Variant chr14-90404693-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1122289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAdExome4 at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CALM1 | NM_006888.6 | c.426C>T | p.Phe142= | synonymous_variant | 6/6 | ENST00000356978.9 | |
CALM1 | NM_001363670.2 | c.429C>T | p.Phe143= | synonymous_variant | 6/6 | ||
CALM1 | NM_001363669.2 | c.318C>T | p.Phe106= | synonymous_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CALM1 | ENST00000356978.9 | c.426C>T | p.Phe142= | synonymous_variant | 6/6 | 1 | NM_006888.6 | P1 | |
ENST00000555853.1 | n.44+499G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152162Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250778Hom.: 1 AF XY: 0.00 AC XY: 0AN XY: 135564
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1457276Hom.: 1 Cov.: 28 AF XY: 0.00000827 AC XY: 6AN XY: 725246
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152280Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74464
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Catecholaminergic polymorphic ventricular tachycardia 4;C4015671:Long QT syndrome 14 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 08, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 27, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at