chr14-90397070-C-T
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_006888.6(CALM1):c.-161C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 692,668 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0074 ( 16 hom., cov: 34)
Exomes 𝑓: 0.00083 ( 5 hom. )
Consequence
CALM1
NM_006888.6 5_prime_UTR_premature_start_codon_gain
NM_006888.6 5_prime_UTR_premature_start_codon_gain
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.253
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 -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
Variant 14-90397070-C-T is Benign according to our data. Variant chr14-90397070-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1219590.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00743 (1131/152166) while in subpopulation AFR AF= 0.0256 (1062/41534). AF 95% confidence interval is 0.0243. There are 16 homozygotes in gnomad4. There are 534 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1131 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CALM1 | NM_006888.6 | c.-161C>T | 5_prime_UTR_premature_start_codon_gain_variant | 1/6 | ENST00000356978.9 | NP_008819.1 | ||
CALM1 | NM_006888.6 | c.-161C>T | 5_prime_UTR_variant | 1/6 | ENST00000356978.9 | NP_008819.1 | ||
CALM1 | NM_001363669.2 | c.-106+412C>T | intron_variant | NP_001350598.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CALM1 | ENST00000356978.9 | c.-161C>T | 5_prime_UTR_premature_start_codon_gain_variant | 1/6 | 1 | NM_006888.6 | ENSP00000349467.4 | |||
CALM1 | ENST00000356978.9 | c.-161C>T | 5_prime_UTR_variant | 1/6 | 1 | NM_006888.6 | ENSP00000349467.4 |
Frequencies
GnomAD3 genomes AF: 0.00739 AC: 1124AN: 152048Hom.: 16 Cov.: 34
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GnomAD4 exome AF: 0.000834 AC: 451AN: 540502Hom.: 5 Cov.: 7 AF XY: 0.000649 AC XY: 187AN XY: 288180
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GnomAD4 genome AF: 0.00743 AC: 1131AN: 152166Hom.: 16 Cov.: 34 AF XY: 0.00718 AC XY: 534AN XY: 74398
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 15, 2018 | - - |
Computational scores
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Benign
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Benign
DANN
Benign
RBP_binding_hub_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at