15-32025256-A-G

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.42

Publications

3 publications found
Variant links:
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 disorder
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
  • epilepsy
    Inheritance: 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
CHRNA7ENST00000636603.1 linkc.-131-5642A>G intron_variant Intron 1 of 9 5 ENSP00000490513.1 A0A1B0GVH2
CHRNA7ENST00000637183.1 linkc.-43+47062A>G intron_variant Intron 1 of 8 5 ENSP00000490365.1 A0A1B0GV43
CHRNA7ENST00000638106.1 linkc.-378-5642A>G intron_variant Intron 1 of 8 5 ENSP00000490413.1 A0A1B0GV86
CHRNA7ENST00000635978.1 linkc.-42-76047A>G intron_variant Intron 1 of 6 5 ENSP00000490778.1 A0A1B0GW52

Frequencies

GnomAD3 genomes
AF:
0.580
AC:
87984
AN:
151818
Hom.:
28884
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.300
Gnomad AMI
AF:
0.704
Gnomad AMR
AF:
0.541
Gnomad ASJ
AF:
0.660
Gnomad EAS
AF:
0.191
Gnomad SAS
AF:
0.693
Gnomad FIN
AF:
0.834
Gnomad MID
AF:
0.601
Gnomad NFE
AF:
0.734
Gnomad OTH
AF:
0.579
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.579
AC:
87978
AN:
151936
Hom.:
28876
Cov.:
32
AF XY:
0.583
AC XY:
43307
AN XY:
74268
show subpopulations
African (AFR)
AF:
0.300
AC:
12432
AN:
41448
American (AMR)
AF:
0.540
AC:
8238
AN:
15258
Ashkenazi Jewish (ASJ)
AF:
0.660
AC:
2288
AN:
3466
East Asian (EAS)
AF:
0.191
AC:
990
AN:
5176
South Asian (SAS)
AF:
0.692
AC:
3323
AN:
4800
European-Finnish (FIN)
AF:
0.834
AC:
8797
AN:
10546
Middle Eastern (MID)
AF:
0.588
AC:
173
AN:
294
European-Non Finnish (NFE)
AF:
0.734
AC:
49883
AN:
67928
Other (OTH)
AF:
0.575
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:
0.670
Hom.:
124552
Bravo
AF:
0.539
Asia WGS
AF:
0.467
AC:
1618
AN:
3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.026
DANN
Benign
0.52
PhyloP100
-2.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs965435; hg19: chr15-32317459; API