15-26909926-A-G
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000810.4(GABRA5):c.498-4877A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,260 control chromosomes in the GnomAD database, including 61,687 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 0.90 ( 61687 hom., cov: 34)
Consequence
GABRA5
NM_000810.4 intron
NM_000810.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.178
Genes affected
GABRA5 (HGNC:4079): (gamma-aminobutyric acid type A receptor subunit alpha5) 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. Transcript variants utilizing three different alternative non-coding first exons have been described. [provided by RefSeq, Jul 2008]
GABRB3 (HGNC:4083): (gamma-aminobutyric acid type A receptor subunit beta3) This gene encodes a member of the ligand-gated ionic channel family. The encoded protein is one the subunits of a multi-subunit chloride channel that serves as the receptor for gamma-aminobutyric acid, a major inhibitory neurotransmitter of the mammalian nervous system. This gene is located on the long arm of chromosome 15 in a cluster with two other genes encoding related subunits of the family. This gene may be associated with the pathogenesis of several disorders including Angelman syndrome, Prader-Willi syndrome, nonsyndromic orofacial clefts, epilepsy and autism. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRA5 | NM_000810.4 | c.498-4877A>G | intron_variant | ENST00000335625.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRA5 | ENST00000335625.10 | c.498-4877A>G | intron_variant | 1 | NM_000810.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.899 AC: 136799AN: 152142Hom.: 61653 Cov.: 34
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GnomAD4 genome ? AF: 0.899 AC: 136886AN: 152260Hom.: 61687 Cov.: 34 AF XY: 0.896 AC XY: 66721AN XY: 74444
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3478
ClinVar
Not reported inComputational scores
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Name
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at