rs181790623
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004519.4(KCNQ3):c.1568+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 1,572,174 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 1 hom. )
Consequence
KCNQ3
NM_004519.4 intron
NM_004519.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.82
Genes affected
KCNQ3 (HGNC:6297): (potassium voltage-gated channel subfamily Q member 3) This gene encodes a protein that functions in the regulation of neuronal excitability. The encoded protein forms an M-channel by associating with the products of the related KCNQ2 or KCNQ5 genes, which both encode integral membrane proteins. M-channel currents are inhibited by M1 muscarinic acetylcholine receptors and are activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of benign familial neonatal convulsions type 2 (BFNC2), also known as epilepsy, benign neonatal type 2 (EBN2). Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 8-132140064-T-C is Benign according to our data. Variant chr8-132140064-T-C is described in ClinVar as [Benign]. Clinvar id is 138043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00122 (186/152152) while in subpopulation AFR AF= 0.00431 (179/41524). AF 95% confidence interval is 0.00379. There are 1 homozygotes in gnomad4. There are 84 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 182 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ3 | NM_004519.4 | c.1568+12A>G | intron_variant | ENST00000388996.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ3 | ENST00000388996.10 | c.1568+12A>G | intron_variant | 1 | NM_004519.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00120 AC: 182AN: 152034Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000338 AC: 74AN: 219108Hom.: 0 AF XY: 0.000257 AC XY: 30AN XY: 116746
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GnomAD4 exome AF: 0.000102 AC: 145AN: 1420022Hom.: 1 Cov.: 28 AF XY: 0.0000882 AC XY: 62AN XY: 703036
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GnomAD4 genome ? AF: 0.00122 AC: 186AN: 152152Hom.: 1 Cov.: 32 AF XY: 0.00113 AC XY: 84AN XY: 74396
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 27, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign neonatal seizures Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 29, 2017 | - - |
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