5-161847209-AG-AGGG
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_000806.5(GABRA1):c.-443_-442dupGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,686 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GABRA1
NM_000806.5 5_prime_UTR
NM_000806.5 5_prime_UTR
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.380
Publications
0 publications found
Genes affected
GABRA1 (HGNC:4075): (gamma-aminobutyric acid type A receptor subunit alpha1) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene cause juvenile myoclonic epilepsy and childhood absence epilepsy type 4. Multiple transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]
GABRA1 Gene-Disease associations (from GenCC):
- developmental and epileptic encephalopathy, 19Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
- epilepsyInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- epilepsy, idiopathic generalized, susceptibility to, 13Inheritance: AD Classification: STRONG Submitted by: G2P
- Dravet syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- juvenile myoclonic epilepsyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000806.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GABRA1 | NM_000806.5 | c.-443_-442dupGG | 5_prime_UTR | Exon 1 of 11 | NP_000797.2 | A8K177 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GABRA1 | ENST00000023897.10 | TSL:1 | c.-443_-442dupGG | 5_prime_UTR | Exon 1 of 11 | ENSP00000023897.6 | P14867 | ||
| GABRA1 | ENST00000638112.1 | TSL:5 | c.-498_-497dupGG | 5_prime_UTR | Exon 1 of 11 | ENSP00000489839.1 | P14867 | ||
| ENSG00000294143 | ENST00000721460.1 | n.71+3309_71+3310dupCC | intron | N/A |
Frequencies
GnomAD3 genomes 0.0000132 AC: 2AN: 151686Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
151686
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 12Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 12
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
12
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
12
African (AFR)
AC:
0
AN:
0
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AF:
AC:
0
AN:
2
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
AC:
0
AN:
10
Other (OTH)
AC:
0
AN:
0
GnomAD4 genome 0.0000132 AC: 2AN: 151686Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74078 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
2
AN:
151686
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74078
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
41194
American (AMR)
AF:
AC:
0
AN:
15224
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3466
East Asian (EAS)
AF:
AC:
0
AN:
5172
South Asian (SAS)
AF:
AC:
0
AN:
4798
European-Finnish (FIN)
AF:
AC:
0
AN:
10580
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67946
Other (OTH)
AF:
AC:
0
AN:
2080
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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