chr4-46977529-C-T
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_000809.4(GABRA4):c.375G>A(p.Thr125=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000843 in 1,612,552 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 (★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000079 ( 0 hom. )
Consequence
GABRA4
NM_000809.4 synonymous
NM_000809.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.630
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
Variant 4-46977529-C-T is Benign according to our data. Variant chr4-46977529-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 734596.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.63 with no splicing effect.
BS2
High AC in GnomAd4 at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRA4 | NM_000809.4 | c.375G>A | p.Thr125= | synonymous_variant | 4/9 | ENST00000264318.4 | |
GABRA4 | NM_001204266.2 | c.318G>A | p.Thr106= | synonymous_variant | 4/9 | ||
GABRA4 | NM_001204267.2 | c.318G>A | p.Thr106= | synonymous_variant | 4/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRA4 | ENST00000264318.4 | c.375G>A | p.Thr125= | synonymous_variant | 4/9 | 1 | NM_000809.4 | P1 | |
GABRA4 | ENST00000502874.1 | c.*145G>A | 3_prime_UTR_variant, NMD_transcript_variant | 3/6 | 5 | ||||
GABRA4 | ENST00000508560.5 | c.*196G>A | 3_prime_UTR_variant, NMD_transcript_variant | 4/9 | 3 | ||||
GABRA4 | ENST00000511523.5 | c.*196G>A | 3_prime_UTR_variant, NMD_transcript_variant | 4/8 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000132 AC: 20AN: 152012Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000291 AC: 73AN: 250954Hom.: 0 AF XY: 0.000192 AC XY: 26AN XY: 135650
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GnomAD4 exome AF: 0.0000794 AC: 116AN: 1460422Hom.: 0 Cov.: 31 AF XY: 0.0000674 AC XY: 49AN XY: 726618
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GnomAD4 genome AF: 0.000131 AC: 20AN: 152130Hom.: 0 Cov.: 31 AF XY: 0.000175 AC XY: 13AN XY: 74356
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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 | Invitae | Apr 02, 2018 | - - |
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