rs191723671
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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.4-10C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 1,606,434 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 0.0015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
CALM1
NM_006888.6 splice_polypyrimidine_tract, intron
NM_006888.6 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0009739
2
Clinical Significance
Conservation
PhyloP100: 1.22
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=-0.4).
BP6
?
Variant 14-90400055-C-G is Benign according to our data. Variant chr14-90400055-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 389903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-90400055-C-G is described in Lovd as [Benign].
BS2
?
High AC in GnomAd4 at 225 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CALM1 | NM_006888.6 | c.4-10C>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000356978.9 | |||
CALM1 | NM_001363669.2 | c.-105-10C>G | splice_polypyrimidine_tract_variant, intron_variant | ||||
CALM1 | NM_001363670.2 | c.7-10C>G | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CALM1 | ENST00000356978.9 | c.4-10C>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_006888.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00147 AC: 223AN: 152108Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000323 AC: 81AN: 250540Hom.: 0 AF XY: 0.000281 AC XY: 38AN XY: 135398
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GnomAD4 exome AF: 0.000137 AC: 199AN: 1454208Hom.: 0 Cov.: 27 AF XY: 0.000116 AC XY: 84AN XY: 724046
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GnomAD4 genome ? AF: 0.00148 AC: 225AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.00137 AC XY: 102AN XY: 74432
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 31, 2021 | - - |
Catecholaminergic polymorphic ventricular tachycardia 4;C4015671:Long QT syndrome 14 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | - - |
Computational scores
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Name
Calibrated prediction
Score
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at