NM_000747.3:c.26T>C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_000747.3(CHRNB1):āc.26T>Cā(p.Leu9Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,609,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_000747.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CHRNB1 | ENST00000306071.7 | c.26T>C | p.Leu9Pro | missense_variant | Exon 1 of 11 | 1 | NM_000747.3 | ENSP00000304290.2 | ||
ENSG00000272884 | ENST00000575331.1 | n.4740T>C | non_coding_transcript_exon_variant | Exon 3 of 3 | 1 | |||||
CHRNB1 | ENST00000572857.5 | c.26T>C | p.Leu9Pro | missense_variant | Exon 1 of 6 | 4 | ENSP00000461402.1 | |||
CHRNB1 | ENST00000574054.1 | n.46T>C | non_coding_transcript_exon_variant | Exon 1 of 2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000424 AC: 1AN: 235750Hom.: 0 AF XY: 0.00000768 AC XY: 1AN XY: 130138
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1457420Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 724994
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74374
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 2A Uncertain:1
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1417212). This variant has not been reported in the literature in individuals affected with CHRNB1-related conditions. This variant is present in population databases (no rsID available, gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 9 of the CHRNB1 protein (p.Leu9Pro). -
not provided Uncertain:1
This observation is not an independent occurrence and has been identified in the same individual by RCIGM, the other laboratory participating in the GEMINI study. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at