4-46250341-T-C
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000807.4(GABRA2):āc.1323A>Gā(p.Leu441=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,610,836 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 Likely benign (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
GABRA2
NM_000807.4 synonymous
NM_000807.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.509
Genes affected
GABRA2 (HGNC:4076): (gamma-aminobutyric acid type A receptor subunit alpha2) 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 4-46250341-T-C is Benign according to our data. Variant chr4-46250341-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1978712.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.509 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRA2 | NM_000807.4 | c.1323A>G | p.Leu441= | synonymous_variant | 10/10 | ENST00000381620.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRA2 | ENST00000381620.9 | c.1323A>G | p.Leu441= | synonymous_variant | 10/10 | 1 | NM_000807.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000660 AC: 1AN: 151612Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459224Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 725964
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GnomAD4 genome AF: 0.00000660 AC: 1AN: 151612Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74018
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 15, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at