chr15-32111732-A-G
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_000746.6(CHRNA7):c.241-58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 995,950 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0074 ( 14 hom., cov: 33)
Exomes 𝑓: 0.00086 ( 4 hom. )
Consequence
CHRNA7
NM_000746.6 intron
NM_000746.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.970
Genes affected
CHRNA7 (HGNC:1960): (cholinergic receptor nicotinic alpha 7 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 thought to be hetero-pentamers composed of homologous subunits. The proposed structure for each subunit 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. The protein encoded by this gene forms a homo-oligomeric channel, displays marked permeability to calcium ions and is a major component of brain nicotinic receptors that are blocked by, and highly sensitive to, alpha-bungarotoxin. Once this receptor binds acetylcholine, it undergoes an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. This gene is located in a region identified as a major susceptibility locus for juvenile myoclonic epilepsy and a chromosomal location involved in the genetic transmission of schizophrenia. An evolutionarily recent partial duplication event in this region results in a hybrid containing sequence from this gene and a novel FAM7A gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 15-32111732-A-G is Benign according to our data. Variant chr15-32111732-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1707251.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00744 (1133/152326) while in subpopulation AFR AF= 0.0252 (1049/41548). AF 95% confidence interval is 0.024. There are 14 homozygotes in gnomad4. There are 539 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1133 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHRNA7 | NM_000746.6 | c.241-58A>G | intron_variant | ENST00000306901.9 | NP_000737.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CHRNA7 | ENST00000306901.9 | c.241-58A>G | intron_variant | 1 | NM_000746.6 | ENSP00000303727.2 |
Frequencies
GnomAD3 genomes AF: 0.00742 AC: 1130AN: 152208Hom.: 14 Cov.: 33
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GnomAD4 exome AF: 0.000863 AC: 728AN: 843624Hom.: 4 Cov.: 11 AF XY: 0.000764 AC XY: 334AN XY: 437172
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GnomAD4 genome AF: 0.00744 AC: 1133AN: 152326Hom.: 14 Cov.: 33 AF XY: 0.00724 AC XY: 539AN XY: 74492
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 21, 2018 | See Variant Classification Assertion Criteria. - |
Computational 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