chr4-47031734-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000812.4(GABRB1):c.80+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,611,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
GABRB1
NM_000812.4 splice_donor_region, intron
NM_000812.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0009818
2
Clinical Significance
Conservation
PhyloP100: 1.36
Genes affected
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GABRB1 | NM_000812.4 | c.80+3G>A | splice_donor_region_variant, intron_variant | ENST00000295454.8 | NP_000803.2 | |||
GABRB1 | XM_017007986.3 | c.80+3G>A | splice_donor_region_variant, intron_variant | XP_016863475.1 | ||||
GABRB1 | XM_024453976.2 | c.-19-180G>A | intron_variant | XP_024309744.1 | ||||
GABRB1 | XM_024453977.2 | c.-19-180G>A | intron_variant | XP_024309745.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GABRB1 | ENST00000295454.8 | c.80+3G>A | splice_donor_region_variant, intron_variant | 1 | NM_000812.4 | ENSP00000295454 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000661 AC: 1AN: 151310Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251258Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135800
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459898Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2AN XY: 726428
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GnomAD4 genome AF: 0.00000661 AC: 1AN: 151310Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73846
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 18, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. This variant has not been reported in the literature in individuals affected with GABRB1-related conditions. This variant is present in population databases (rs779124452, gnomAD 0.003%). This sequence change falls in intron 1 of the GABRB1 gene. It does not directly change the encoded amino acid sequence of the GABRB1 protein. It affects a nucleotide within the consensus splice site. - |
GABRB1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 28, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at