chr15-27520009-T-C
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_033223.5(GABRG3):c.750T>C(p.Ser250=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,578,080 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0088 ( 23 hom., cov: 32)
Exomes 𝑓: 0.00085 ( 13 hom. )
Consequence
GABRG3
NM_033223.5 synonymous
NM_033223.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0960
Genes affected
GABRG3 (HGNC:4088): (gamma-aminobutyric acid type A receptor subunit gamma3) This gene encodes a gamma-aminobutyric acid (GABA) receptor. 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. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. The protein encoded by this gene is a gamma subunit, which contains the benzodiazepine binding site. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Aug 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 15-27520009-T-C is Benign according to our data. Variant chr15-27520009-T-C is described in ClinVar as [Benign]. Clinvar id is 787957.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.096 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00877 (1335/152286) while in subpopulation AFR AF= 0.0309 (1283/41556). AF 95% confidence interval is 0.0295. There are 23 homozygotes in gnomad4. There are 603 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 23 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRG3 | NM_033223.5 | c.750T>C | p.Ser250= | synonymous_variant | 7/10 | ENST00000615808.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRG3 | ENST00000615808.5 | c.750T>C | p.Ser250= | synonymous_variant | 7/10 | 1 | NM_033223.5 | P1 | |
ENST00000556642.1 | n.85+21104A>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00876 AC: 1333AN: 152168Hom.: 23 Cov.: 32
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GnomAD3 exomes AF: 0.00223 AC: 450AN: 201960Hom.: 5 AF XY: 0.00169 AC XY: 182AN XY: 107754
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GnomAD4 exome AF: 0.000851 AC: 1214AN: 1425794Hom.: 13 Cov.: 29 AF XY: 0.000739 AC XY: 522AN XY: 706066
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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 | Dec 31, 2019 | - - |
Computational scores
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Name
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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