rs3811993
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_000811.3(GABRA6):c.560C>T(p.Thr187Met) variant causes a missense change. The variant allele was found at a frequency of 0.0136 in 1,608,520 control chromosomes in the GnomAD database, including 278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. T187T) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.010 ( 10 hom., cov: 32)
Exomes 𝑓: 0.014 ( 268 hom. )
Consequence
GABRA6
NM_000811.3 missense
NM_000811.3 missense
Scores
1
6
11
Clinical Significance
Conservation
PhyloP100: 4.82
Genes affected
GABRA6 (HGNC:4080): (gamma-aminobutyric acid type A receptor subunit alpha6) 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. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.015738577).
BP6
?
Variant 5-161689666-C-T is Benign according to our data. Variant chr5-161689666-C-T is described in ClinVar as [Benign]. Clinvar id is 477866.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0104 (1581/152146) while in subpopulation SAS AF= 0.0472 (228/4828). AF 95% confidence interval is 0.0422. There are 10 homozygotes in gnomad4. There are 838 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 10 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRA6 | NM_000811.3 | c.560C>T | p.Thr187Met | missense_variant | 6/9 | ENST00000274545.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRA6 | ENST00000274545.10 | c.560C>T | p.Thr187Met | missense_variant | 6/9 | 1 | NM_000811.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0104 AC: 1582AN: 152028Hom.: 10 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0154 AC: 3853AN: 250646Hom.: 66 AF XY: 0.0175 AC XY: 2378AN XY: 135656
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GnomAD4 exome AF: 0.0140 AC: 20324AN: 1456374Hom.: 268 Cov.: 31 AF XY: 0.0150 AC XY: 10849AN XY: 724746
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GnomAD4 genome ? AF: 0.0104 AC: 1581AN: 152146Hom.: 10 Cov.: 32 AF XY: 0.0113 AC XY: 838AN XY: 74364
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ESP6500AA
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ExAC
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1874
Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Childhood absence epilepsy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;D;D;D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
D;.;.;.
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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