1-40819415-T-C
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_004700.4(KCNQ4):āc.777T>Cā(p.Ala259=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 1,613,444 control chromosomes in the GnomAD database, including 391,549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. A259A) has been classified as Likely benign.
Frequency
Consequence
NM_004700.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ4 | NM_004700.4 | c.777T>C | p.Ala259= | synonymous_variant | 5/14 | ENST00000347132.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ4 | ENST00000347132.10 | c.777T>C | p.Ala259= | synonymous_variant | 5/14 | 1 | NM_004700.4 | P2 | |
KCNQ4 | ENST00000509682.6 | c.777T>C | p.Ala259= | synonymous_variant | 5/13 | 5 | A1 | ||
KCNQ4 | ENST00000443478.3 | c.465T>C | p.Ala155= | synonymous_variant | 4/13 | 5 | |||
KCNQ4 | ENST00000506017.1 | n.96T>C | non_coding_transcript_exon_variant | 2/11 | 2 |
Frequencies
GnomAD3 genomes AF: 0.652 AC: 98868AN: 151664Hom.: 32894 Cov.: 30
GnomAD3 exomes AF: 0.646 AC: 162346AN: 251388Hom.: 53818 AF XY: 0.651 AC XY: 88445AN XY: 135876
GnomAD4 exome AF: 0.696 AC: 1017384AN: 1461662Hom.: 358645 Cov.: 56 AF XY: 0.694 AC XY: 504564AN XY: 727158
GnomAD4 genome AF: 0.652 AC: 98918AN: 151782Hom.: 32904 Cov.: 30 AF XY: 0.646 AC XY: 47913AN XY: 74178
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2017 | 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, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Ala259Ala in Exon 05 of KCNQ4: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 42.4% (1584/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs4660468). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Autosomal dominant nonsyndromic hearing loss 2A Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at