chr12-4910145-CGA-C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_000217.3(KCNA1):c.-861_-860del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 152,274 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0024 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KCNA1
NM_000217.3 5_prime_UTR
NM_000217.3 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.590
Genes affected
KCNA1 (HGNC:6218): (potassium voltage-gated channel subfamily A member 1) This gene encodes a voltage-gated delayed potassium channel that is phylogenetically related to the Drosophila Shaker channel. The encoded protein has six putative transmembrane segments (S1-S6), and the loop between S5 and S6 forms the pore and contains the conserved selectivity filter motif (GYGD). The functional channel is a homotetramer. The N-terminus of the channel is associated with beta subunits that can modify the inactivation properties of the channel as well as affect expression levels. The C-terminus of the channel is complexed to a PDZ domain protein that is responsible for channel targeting. Mutations in this gene have been associated with myokymia with periodic ataxia (AEMK). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP6
?
Variant 12-4910145-CGA-C is Benign according to our data. Variant chr12-4910145-CGA-C is described in ClinVar as [Likely_benign]. Clinvar id is 309127.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00235 (358/152274) while in subpopulation NFE AF= 0.00334 (227/68014). AF 95% confidence interval is 0.00298. There are 3 homozygotes in gnomad4. There are 161 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 358 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNA1 | NM_000217.3 | c.-861_-860del | 5_prime_UTR_variant | 1/2 | ENST00000382545.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNA1 | ENST00000382545.5 | c.-861_-860del | 5_prime_UTR_variant | 1/2 | 4 | NM_000217.3 | P1 | ||
ENST00000640877.1 | n.285_286del | non_coding_transcript_exon_variant | 1/9 | 5 | |||||
ENST00000638821.1 | n.251_252del | non_coding_transcript_exon_variant | 1/2 | 5 | |||||
ENST00000640962.1 | n.47_48del | non_coding_transcript_exon_variant | 1/8 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00235 AC: 358AN: 152156Hom.: 3 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 478Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 292
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary episodic ataxia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Myokymia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at