rs200426006
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004700.4(KCNQ4):c.1292+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000467 in 1,603,776 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0019 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00031 ( 3 hom. )
Consequence
KCNQ4
NM_004700.4 intron
NM_004700.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.543
Genes affected
KCNQ4 (HGNC:6298): (potassium voltage-gated channel subfamily Q member 4) The protein encoded by this gene forms a potassium channel that is thought to play a critical role in the regulation of neuronal excitability, particularly in sensory cells of the cochlea. The current generated by this channel is inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. The encoded protein can form a homomultimeric potassium channel or possibly a heteromultimeric channel in association with the protein encoded by the KCNQ3 gene. Defects in this gene are a cause of nonsyndromic sensorineural deafness type 2 (DFNA2), an autosomal dominant form of progressive hearing loss. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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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=-0.66).
BP6
?
Variant 1-40824270-G-A is Benign according to our data. Variant chr1-40824270-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227465.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 = 0.00192 (292/152296) while in subpopulation AFR AF= 0.00626 (260/41566). AF 95% confidence interval is 0.00563. There are 0 homozygotes in gnomad4. There are 142 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 292 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ4 | NM_004700.4 | c.1292+12G>A | intron_variant | ENST00000347132.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ4 | ENST00000347132.10 | c.1292+12G>A | intron_variant | 1 | NM_004700.4 | P2 | |||
KCNQ4 | ENST00000443478.3 | c.816+1868G>A | intron_variant | 5 | |||||
KCNQ4 | ENST00000509682.6 | c.1130+1868G>A | intron_variant | 5 | A1 | ||||
KCNQ4 | ENST00000506017.1 | n.611+12G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00191 AC: 291AN: 152178Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000697 AC: 152AN: 218194Hom.: 1 AF XY: 0.000703 AC XY: 85AN XY: 120956
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GnomAD4 exome AF: 0.000315 AC: 457AN: 1451480Hom.: 3 Cov.: 33 AF XY: 0.000369 AC XY: 266AN XY: 721570
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GnomAD4 genome ? AF: 0.00192 AC: 292AN: 152296Hom.: 0 Cov.: 33 AF XY: 0.00191 AC XY: 142AN XY: 74468
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 19, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | 1292+12G>A in Intron 09 of KCNQ4: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 0.5% (17/3628) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS). - |
Autosomal dominant nonsyndromic hearing loss 2A Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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