rs2292977
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000742.4(CHRNA2):c.*511G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CHRNA2
NM_000742.4 3_prime_UTR
NM_000742.4 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.21
Genes affected
CHRNA2 (HGNC:1956): (cholinergic receptor nicotinic alpha 2 subunit) Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels formed by a pentameric arrangement of alpha and beta subunits to create distinct muscle and neuronal receptors. Neuronal receptors are found throughout the peripheral and central nervous system where they are involved in fast synaptic transmission. This gene encodes an alpha subunit that is widely expressed in the brain. The proposed structure for nAChR subunits is a conserved N-terminal extracellular domain followed by three conserved transmembrane domains, a variable cytoplasmic loop, a fourth conserved transmembrane domain, and a short C-terminal extracellular region. Mutations in this gene cause autosomal dominant nocturnal frontal lobe epilepsy type 4. Single nucleotide polymorphisms (SNPs) in this gene have been associated with nicotine dependence. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA2 | NM_000742.4 | c.*511G>T | 3_prime_UTR_variant | 7/7 | ENST00000407991.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA2 | ENST00000407991.3 | c.*511G>T | 3_prime_UTR_variant | 7/7 | 5 | NM_000742.4 | P2 | ||
CHRNA2 | ENST00000520600.1 | n.926G>T | non_coding_transcript_exon_variant | 2/2 | 1 | ||||
CHRNA2 | ENST00000523695.5 | c.*1503G>T | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 1 | ||||
CHRNA2 | ENST00000520933.7 | c.*511G>T | 3_prime_UTR_variant | 7/7 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152060Hom.: 0 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000329 AC: 1AN: 30358Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 16140
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152060Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74260
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ClinVar
Not reported inComputational scores
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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