1-40784135-G-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_004700.4(KCNQ4):c.42G>T(p.Pro14Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000348 in 976,386 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000055 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 1 hom. )
Consequence
KCNQ4
NM_004700.4 synonymous
NM_004700.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.797
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 -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
Variant 1-40784135-G-T is Benign according to our data. Variant chr1-40784135-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3705129.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.797 with no splicing effect.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000313 (26/831648) while in subpopulation MID AF= 0.00164 (3/1828). AF 95% confidence interval is 0.000447. There are 1 homozygotes in gnomad4_exome. There are 12 alleles in male gnomad4_exome subpopulation. Median coverage is 12. This position pass quality control queck.
BS2
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNQ4 | NM_004700.4 | c.42G>T | p.Pro14Pro | synonymous_variant | Exon 1 of 14 | ENST00000347132.10 | NP_004691.2 | |
KCNQ4 | NM_172163.3 | c.42G>T | p.Pro14Pro | synonymous_variant | Exon 1 of 13 | NP_751895.1 | ||
KCNQ4 | XM_047434057.1 | c.42G>T | p.Pro14Pro | synonymous_variant | Exon 1 of 13 | XP_047290013.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNQ4 | ENST00000347132.10 | c.42G>T | p.Pro14Pro | synonymous_variant | Exon 1 of 14 | 1 | NM_004700.4 | ENSP00000262916.6 | ||
KCNQ4 | ENST00000509682.6 | c.42G>T | p.Pro14Pro | synonymous_variant | Exon 1 of 13 | 5 | ENSP00000423756.2 |
Frequencies
GnomAD3 genomes AF: 0.0000553 AC: 8AN: 144738Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000360 AC: 6AN: 16682Hom.: 1 AF XY: 0.000295 AC XY: 3AN XY: 10160
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GnomAD4 exome AF: 0.0000313 AC: 26AN: 831648Hom.: 1 Cov.: 12 AF XY: 0.0000301 AC XY: 12AN XY: 398264
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GnomAD4 genome AF: 0.0000553 AC: 8AN: 144738Hom.: 0 Cov.: 32 AF XY: 0.0000284 AC XY: 2AN XY: 70390
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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
Mar 01, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at