rs4954
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000749.5(CHRNB3):c.1242+104G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.931 in 1,053,734 control chromosomes in the GnomAD database, including 458,169 homozygotes. 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 0.90 ( 61451 hom., cov: 33)
Exomes 𝑓: 0.94 ( 396718 hom. )
Consequence
CHRNB3
NM_000749.5 intron
NM_000749.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.957
Genes affected
CHRNB3 (HGNC:1963): (cholinergic receptor nicotinic beta 3 subunit) The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The nAChRs are (hetero)pentamers composed of homologous subunits. The subunits that make up the muscle and neuronal forms of nAChRs are encoded by separate genes and have different primary structure. There are several subtypes of neuronal nAChRs that vary based on which homologous subunits are arranged around the central channel. They are classified as alpha-subunits if, like muscle alpha-1 (MIM 100690), they have a pair of adjacent cysteines as part of the presumed acetylcholine binding site. Subunits lacking these cysteine residues are classified as beta-subunits (Groot Kormelink and Luyten, 1997 [PubMed 9009220]). Elliott et al. (1996) [PubMed 8906617] stated that the proposed structure for each subunit is a conserved N-terminal extracellular domain followed by 3 conserved transmembrane domains, a variable cytoplasmic loop, a fourth conserved transmembrane domain, and a short C-terminal extracellular region.[supplied by OMIM, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNB3 | NM_000749.5 | c.1242+104G>A | intron_variant | ENST00000289957.3 | |||
CHRNB3 | NM_001347717.2 | c.1020+104G>A | intron_variant | ||||
CHRNB3 | XM_011544390.3 | c.855+104G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNB3 | ENST00000289957.3 | c.1242+104G>A | intron_variant | 1 | NM_000749.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.896 AC: 136220AN: 152084Hom.: 61416 Cov.: 33
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GnomAD4 exome AF: 0.937 AC: 845117AN: 901532Hom.: 396718 AF XY: 0.937 AC XY: 423330AN XY: 451726
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GnomAD4 genome ? AF: 0.896 AC: 136302AN: 152202Hom.: 61451 Cov.: 33 AF XY: 0.895 AC XY: 66618AN XY: 74418
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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