4-46993643-G-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000809.4(GABRA4):c.-219C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000024 in 416,898 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 0.0000024 ( 0 hom. )
Consequence
GABRA4
NM_000809.4 upstream_gene
NM_000809.4 upstream_gene
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.53
Publications
8 publications found
Genes affected
GABRA4 (HGNC:4078): (gamma-aminobutyric acid type A receptor subunit alpha4) Gamma-aminobutyric acid (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. At least 16 distinct subunits of GABA-A receptors have been identified. This gene encodes subunit alpha-4, which is involved in the etiology of autism and eventually increases autism risk through interaction with another subunit, gamma-aminobutyric acid receptor beta-1 (GABRB1). Alternatively spliced transcript variants encoding different isoforms have been found in this gene.[provided by RefSeq, Feb 2011]
GABRB1 (HGNC:4081): (gamma-aminobutyric acid type A receptor subunit beta1) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes GABA A receptor, beta 1 subunit. It is mapped to chromosome 4p12 in a cluster comprised of genes encoding alpha 4, alpha 2 and gamma 1 subunits of the GABA A receptor. Alteration of this gene is implicated in the pathogenetics of schizophrenia. [provided by RefSeq, Jul 2008]
GABRB1 Gene-Disease associations (from GenCC):
- developmental and epileptic encephalopathy, 45Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000240 AC: 1AN: 416898Hom.: 0 Cov.: 3 AF XY: 0.00000453 AC XY: 1AN XY: 220862 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
416898
Hom.:
Cov.:
3
AF XY:
AC XY:
1
AN XY:
220862
show subpopulations
African (AFR)
AF:
AC:
0
AN:
11722
American (AMR)
AF:
AC:
0
AN:
18640
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
12672
East Asian (EAS)
AF:
AC:
0
AN:
27992
South Asian (SAS)
AF:
AC:
1
AN:
46300
European-Finnish (FIN)
AF:
AC:
0
AN:
25504
Middle Eastern (MID)
AF:
AC:
0
AN:
1820
European-Non Finnish (NFE)
AF:
AC:
0
AN:
248458
Other (OTH)
AF:
AC:
0
AN:
23790
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.875
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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