chr5-161294141-T-A
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_001371727.1(GABRB2):c.1479A>T(p.Ile493=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,918 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 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
GABRB2
NM_001371727.1 synonymous
NM_001371727.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0530
Genes affected
GABRB2 (HGNC:4082): (gamma-aminobutyric acid type A receptor subunit beta2) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes GABA A receptor, beta 2 subunit. It is mapped to chromosome 5q34 in a cluster comprised of genes encoding alpha 1 and gamma 2 subunits of the GABA A receptor. Alternative splicing of this gene generates 2 transcript variants, differing by a 114 bp insertion. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 5-161294141-T-A is Benign according to our data. Variant chr5-161294141-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 464937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.053 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000112 (17/152104) while in subpopulation AMR AF= 0.000851 (13/15272). AF 95% confidence interval is 0.000503. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 17 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRB2 | NM_001371727.1 | c.1479A>T | p.Ile493= | synonymous_variant | 10/10 | ENST00000393959.6 | |
GABRB2 | NM_021911.3 | c.1479A>T | p.Ile493= | synonymous_variant | 11/11 | ||
GABRB2 | NM_000813.3 | c.1365A>T | p.Ile455= | synonymous_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRB2 | ENST00000393959.6 | c.1479A>T | p.Ile493= | synonymous_variant | 10/10 | 1 | NM_001371727.1 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152104Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251364Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135838
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461814Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 727212
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GnomAD4 genome AF: 0.000112 AC: 17AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12AN XY: 74296
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 02, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Intellectual disability Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at