chr4-46965099-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_000809.4(GABRA4):c.1005C>T(p.Ile335=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000558 in 1,612,070 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00082 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00053 ( 10 hom. )
Consequence
GABRA4
NM_000809.4 synonymous
NM_000809.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.34
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 -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
Variant 4-46965099-G-A is Benign according to our data. Variant chr4-46965099-G-A is described in ClinVar as [Benign]. Clinvar id is 724381.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.34 with no splicing effect.
BS2
?
High AC in GnomAd at 124 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRA4 | NM_000809.4 | c.1005C>T | p.Ile335= | synonymous_variant | 8/9 | ENST00000264318.4 | |
GABRA4 | NM_001204266.2 | c.948C>T | p.Ile316= | synonymous_variant | 8/9 | ||
GABRA4 | NM_001204267.2 | c.795C>T | p.Ile265= | synonymous_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRA4 | ENST00000264318.4 | c.1005C>T | p.Ile335= | synonymous_variant | 8/9 | 1 | NM_000809.4 | P1 | |
GABRA4 | ENST00000508560.5 | c.*826C>T | 3_prime_UTR_variant, NMD_transcript_variant | 8/9 | 3 | ||||
GABRA4 | ENST00000511523.5 | c.*673C>T | 3_prime_UTR_variant, NMD_transcript_variant | 7/8 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000817 AC: 124AN: 151688Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00113 AC: 283AN: 250232Hom.: 4 AF XY: 0.00111 AC XY: 150AN XY: 135244
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GnomAD4 exome AF: 0.000531 AC: 776AN: 1460264Hom.: 10 Cov.: 31 AF XY: 0.000540 AC XY: 392AN XY: 726448
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GnomAD4 genome ? AF: 0.000817 AC: 124AN: 151806Hom.: 0 Cov.: 33 AF XY: 0.00121 AC XY: 90AN XY: 74166
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 20, 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