chr1-40824154-C-T
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_004700.4(KCNQ4):c.1188C>T(p.Pro396Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,568,878 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_004700.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNQ4 | ENST00000347132.10 | c.1188C>T | p.Pro396Pro | synonymous_variant | Exon 9 of 14 | 1 | NM_004700.4 | ENSP00000262916.6 | ||
KCNQ4 | ENST00000509682.6 | c.1130+1752C>T | intron_variant | Intron 8 of 12 | 5 | ENSP00000423756.2 | ||||
KCNQ4 | ENST00000443478.3 | c.815+1752C>T | intron_variant | Intron 7 of 12 | 5 | ENSP00000406735.3 | ||||
KCNQ4 | ENST00000506017.1 | n.507C>T | non_coding_transcript_exon_variant | Exon 6 of 11 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00212 AC: 323AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00186 AC: 321AN: 172394Hom.: 1 AF XY: 0.00198 AC XY: 186AN XY: 93714
GnomAD4 exome AF: 0.00327 AC: 4630AN: 1416520Hom.: 12 Cov.: 33 AF XY: 0.00308 AC XY: 2157AN XY: 700704
GnomAD4 genome AF: 0.00212 AC: 323AN: 152358Hom.: 0 Cov.: 33 AF XY: 0.00192 AC XY: 143AN XY: 74494
ClinVar
Submissions by phenotype
not provided Benign:5
KCNQ4: BP4, BS2 -
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This variant is associated with the following publications: (PMID: 10571947) -
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not specified Benign:2
p.Pro396Pro in exon 09 of KCNQ4: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 0.7% (55/8302) of E uropean chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broad institute.org; dbSNP rs189541861). -
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Autosomal dominant nonsyndromic hearing loss 2A Benign:1
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KCNQ4-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at