15-32025256-A-G
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
The ENST00000636603.1(CHRNA7):c.-131-5642A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,936 control chromosomes in the GnomAD database, including 28,876 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 0.58 ( 28876 hom., cov: 32)
Consequence
CHRNA7
ENST00000636603.1 intron
ENST00000636603.1 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.42
Publications
3 publications found
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]
CHRNA7 Gene-Disease associations (from GenCC):
- complex neurodevelopmental disorderInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
- epilepsyInheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.03).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CHRNA7 | ENST00000636603.1 | c.-131-5642A>G | intron_variant | Intron 1 of 9 | 5 | ENSP00000490513.1 | ||||
CHRNA7 | ENST00000637183.1 | c.-43+47062A>G | intron_variant | Intron 1 of 8 | 5 | ENSP00000490365.1 | ||||
CHRNA7 | ENST00000638106.1 | c.-378-5642A>G | intron_variant | Intron 1 of 8 | 5 | ENSP00000490413.1 | ||||
CHRNA7 | ENST00000635978.1 | c.-42-76047A>G | intron_variant | Intron 1 of 6 | 5 | ENSP00000490778.1 |
Frequencies
GnomAD3 genomes AF: 0.580 AC: 87984AN: 151818Hom.: 28884 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
87984
AN:
151818
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.579 AC: 87978AN: 151936Hom.: 28876 Cov.: 32 AF XY: 0.583 AC XY: 43307AN XY: 74268 show subpopulations
GnomAD4 genome
AF:
AC:
87978
AN:
151936
Hom.:
Cov.:
32
AF XY:
AC XY:
43307
AN XY:
74268
show subpopulations
African (AFR)
AF:
AC:
12432
AN:
41448
American (AMR)
AF:
AC:
8238
AN:
15258
Ashkenazi Jewish (ASJ)
AF:
AC:
2288
AN:
3466
East Asian (EAS)
AF:
AC:
990
AN:
5176
South Asian (SAS)
AF:
AC:
3323
AN:
4800
European-Finnish (FIN)
AF:
AC:
8797
AN:
10546
Middle Eastern (MID)
AF:
AC:
173
AN:
294
European-Non Finnish (NFE)
AF:
AC:
49883
AN:
67928
Other (OTH)
AF:
AC:
1212
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1539
3078
4618
6157
7696
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
722
1444
2166
2888
3610
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1618
AN:
3462
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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