5-162067718-C-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The ENST00000639111.2(GABRG2):c.-282C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 609,246 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00017 ( 0 hom. )
Consequence
GABRG2
ENST00000639111.2 5_prime_UTR
ENST00000639111.2 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.362
Genes affected
GABRG2 (HGNC:4087): (gamma-aminobutyric acid type A receptor subunit gamma2) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammlian brain, where it acts at GABA-A receptors, which are ligand-gated chloride channels. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene have been associated with epilepsy and febrile seizures. Multiple transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
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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=-0.83).
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000118 (18/151998) while in subpopulation AMR AF= 0.000459 (7/15248). AF 95% confidence interval is 0.000215. There are 0 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High AC in GnomAd4 at 18 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GABRG2 | NM_000816.3 | c.-282C>T | 5_prime_UTR_variant | 1/9 | NP_000807.2 | |||
GABRG2 | NM_001375339.1 | c.-282C>T | 5_prime_UTR_variant | 1/10 | NP_001362268.1 | |||
GABRG2 | NM_001375340.1 | c.-282C>T | 5_prime_UTR_variant | 1/9 | NP_001362269.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GABRG2 | ENST00000639111.2 | c.-282C>T | 5_prime_UTR_variant | 1/9 | 1 | ENSP00000492125 | P3 | |||
GABRG2 | ENST00000638772.1 | c.-282C>T | 5_prime_UTR_variant | 1/8 | 5 | ENSP00000491557 | ||||
GABRG2 | ENST00000639384.1 | c.-282C>T | 5_prime_UTR_variant | 1/9 | 5 | ENSP00000491240 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 151998Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.000166 AC: 76AN: 457248Hom.: 0 Cov.: 0 AF XY: 0.000148 AC XY: 36AN XY: 242540
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GnomAD4 genome AF: 0.000118 AC: 18AN: 151998Hom.: 0 Cov.: 31 AF XY: 0.000148 AC XY: 11AN XY: 74242
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Epilepsy, childhood absence 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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