8-27460342-AG-A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000742.4(CHRNA2):​c.*1286delC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00069 in 152,102 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00069 ( 2 hom., cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CHRNA2
NM_000742.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.907

Publications

0 publications found
Variant links:
Genes affected
CHRNA2 (HGNC:1956): (cholinergic receptor nicotinic alpha 2 subunit) Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels formed by a pentameric arrangement of alpha and beta subunits to create distinct muscle and neuronal receptors. Neuronal receptors are found throughout the peripheral and central nervous system where they are involved in fast synaptic transmission. This gene encodes an alpha subunit that is widely expressed in the brain. The proposed structure for nAChR subunits 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. Mutations in this gene cause autosomal dominant nocturnal frontal lobe epilepsy type 4. Single nucleotide polymorphisms (SNPs) in this gene have been associated with nicotine dependence. [provided by RefSeq, Nov 2009]
CHRNA2 Gene-Disease associations (from GenCC):
  • autosomal dominant nocturnal frontal lobe epilepsy 4
    Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Illumina, Labcorp Genetics (formerly Invitae)
  • autosomal dominant nocturnal frontal lobe epilepsy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • familial sleep-related hypermotor epilepsy
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen
  • benign familial infantile epilepsy
    Inheritance: AD 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 -10 ACMG points.

BP6
Variant 8-27460342-AG-A is Benign according to our data. Variant chr8-27460342-AG-A is described in ClinVar as [Likely_benign]. Clinvar id is 362672.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00069 (105/152102) while in subpopulation EAS AF = 0.0186 (96/5150). AF 95% confidence interval is 0.0156. There are 2 homozygotes in GnomAd4. There are 61 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
BS2
High AC in GnomAd4 at 105 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHRNA2NM_000742.4 linkc.*1286delC 3_prime_UTR_variant Exon 7 of 7 ENST00000407991.3 NP_000733.2 Q15822-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHRNA2ENST00000407991.3 linkc.*1286delC 3_prime_UTR_variant Exon 7 of 7 5 NM_000742.4 ENSP00000385026.1 Q15822-1
CHRNA2ENST00000520600.1 linkn.*233delC downstream_gene_variant 1

Frequencies

GnomAD3 genomes
AF:
0.000684
AC:
104
AN:
151984
Hom.:
2
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0184
Gnomad SAS
AF:
0.00146
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
58
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
30
African (AFR)
AF:
0.00
AC:
0
AN:
4
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AF:
0.00
AC:
0
AN:
2
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
8
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
38
Other (OTH)
AF:
0.00
AC:
0
AN:
4
GnomAD4 genome
AF:
0.000690
AC:
105
AN:
152102
Hom.:
2
Cov.:
31
AF XY:
0.000820
AC XY:
61
AN XY:
74352
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41502
American (AMR)
AF:
0.00
AC:
0
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3466
East Asian (EAS)
AF:
0.0186
AC:
96
AN:
5150
South Asian (SAS)
AF:
0.00146
AC:
7
AN:
4806
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10594
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67972
Other (OTH)
AF:
0.000473
AC:
1
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
4
8
13
17
21
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
4
8
12
16
20
<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:
0.00
Hom.:
0
Bravo
AF:
0.00105
Asia WGS
AF:
0.00491
AC:
18
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Familial sleep-related hypermotor epilepsy Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
-0.91
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs199764226; hg19: chr8-27317859; API