rs45617636
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001161352.2(KCNMA1):c.1320C>T(p.Ile440=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,610,452 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0015 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0020 ( 3 hom. )
Consequence
KCNMA1
NM_001161352.2 synonymous
NM_001161352.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.132
Genes affected
KCNMA1 (HGNC:6284): (potassium calcium-activated channel subfamily M alpha 1) This gene encodes the alpha subunit of calcium-activated BK channel. The encoded protein is involved in several physiological processes including smooth muscle contraction, neurotransmitter release and neuronal excitability. Mutations in this gene are associated with a spectrum of neurological disorders including Paroxysmal Nonkinesigenic Dyskinesia 3, Idiopathic Generalized Epilepsy 16 and Liang-Wang syndrome. [provided by RefSeq, Aug 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
Variant 10-77090414-G-A is Benign according to our data. Variant chr10-77090414-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 289603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-77090414-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.132 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00146 (222/152236) while in subpopulation NFE AF= 0.00241 (164/68020). AF 95% confidence interval is 0.00211. There are 1 homozygotes in gnomad4. There are 106 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 3 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNMA1 | NM_001161352.2 | c.1320C>T | p.Ile440= | synonymous_variant | 10/28 | ENST00000286628.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNMA1 | ENST00000286628.14 | c.1320C>T | p.Ile440= | synonymous_variant | 10/28 | 1 | NM_001161352.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00146 AC: 222AN: 152118Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00198 AC: 497AN: 251288Hom.: 1 AF XY: 0.00210 AC XY: 285AN XY: 135812
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GnomAD4 exome AF: 0.00203 AC: 2966AN: 1458216Hom.: 3 Cov.: 30 AF XY: 0.00202 AC XY: 1466AN XY: 725718
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GnomAD4 genome ? AF: 0.00146 AC: 222AN: 152236Hom.: 1 Cov.: 33 AF XY: 0.00142 AC XY: 106AN XY: 74430
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Generalized epilepsy-paroxysmal dyskinesia syndrome Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Oct 05, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Aug 02, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 19, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 29, 2016 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 28, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | KCNMA1: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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