rs17621256
Variant names:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_000749.5(CHRNB3):c.1243-1719C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 152,122 control chromosomes in the GnomAD database, including 46 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 0.020 ( 46 hom., cov: 30)
Consequence
CHRNB3
NM_000749.5 intron
NM_000749.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.54
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=-0.91).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0196 (2987/152122) while in subpopulation NFE AF= 0.0309 (2098/67996). AF 95% confidence interval is 0.0298. There are 46 homozygotes in gnomad4. There are 1413 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 46 AR gene
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CHRNB3 | NM_000749.5 | c.1243-1719C>A | intron_variant | Intron 5 of 5 | ENST00000289957.3 | NP_000740.1 | ||
| CHRNB3 | NM_001347717.2 | c.1021-1719C>A | intron_variant | Intron 6 of 6 | NP_001334646.1 | |||
| CHRNB3 | XM_011544390.3 | c.856-1719C>A | intron_variant | Intron 3 of 3 | XP_011542692.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.0196 AC: 2982AN: 152006Hom.: 46 Cov.: 30
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.0196 AC: 2987AN: 152122Hom.: 46 Cov.: 30 AF XY: 0.0190 AC XY: 1413AN XY: 74344
GnomAD4 genome
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at