chr17-4899468-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000521575(C17orf107):c.-295G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000825 in 1,587,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000521575 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHRNE | NM_000080.4 | c.1032C>T | p.His344His | splice_region_variant, synonymous_variant | Exon 9 of 12 | ENST00000649488.2 | NP_000071.1 | |
CHRNE | XM_017024115.2 | c.996C>T | p.His332His | splice_region_variant, synonymous_variant | Exon 10 of 13 | XP_016879604.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152136Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000190 AC: 39AN: 205554Hom.: 0 AF XY: 0.000180 AC XY: 20AN XY: 111276
GnomAD4 exome AF: 0.0000885 AC: 127AN: 1435752Hom.: 0 Cov.: 34 AF XY: 0.0000801 AC XY: 57AN XY: 711656
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152136Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74316
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 4A Uncertain:1
This sequence change affects codon 344 of the CHRNE mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CHRNE protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs144047383, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with CHRNE-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at