rs144313756
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_005458.8(GABBR2):c.1473C>T(p.Leu491=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000844 in 1,613,668 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00081 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00085 ( 2 hom. )
Consequence
GABBR2
NM_005458.8 synonymous
NM_005458.8 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0800
Genes affected
GABBR2 (HGNC:4507): (gamma-aminobutyric acid type B receptor subunit 2) The multi-pass membrane protein encoded by this gene belongs to the G-protein coupled receptor 3 family and GABA-B receptor subfamily. The GABA-B receptors inhibit neuronal activity through G protein-coupled second-messenger systems, which regulate the release of neurotransmitters, and the activity of ion channels and adenylyl cyclase. This receptor subunit forms an active heterodimeric complex with GABA-B receptor subunit 1, neither of which is effective on its own. Allelic variants of this gene have been associated with nicotine dependence.[provided by RefSeq, Jan 2010]
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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=-0.42).
BP6
?
Variant 9-98388910-G-A is Benign according to our data. Variant chr9-98388910-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 462124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.08 with no splicing effect.
BS2
?
High AC in GnomAd4 at 124 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABBR2 | NM_005458.8 | c.1473C>T | p.Leu491= | synonymous_variant | 10/19 | ENST00000259455.4 | |
GABBR2 | XM_017015331.3 | c.1179C>T | p.Leu393= | synonymous_variant | 9/18 | ||
GABBR2 | XM_005252316.6 | c.699C>T | p.Leu233= | synonymous_variant | 8/17 | ||
GABBR2 | XM_017015332.3 | c.699C>T | p.Leu233= | synonymous_variant | 7/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABBR2 | ENST00000259455.4 | c.1473C>T | p.Leu491= | synonymous_variant | 10/19 | 1 | NM_005458.8 | P1 | |
GABBR2 | ENST00000637410.1 | n.1251C>T | non_coding_transcript_exon_variant | 10/19 | 5 | ||||
GABBR2 | ENST00000634314.1 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000815 AC: 124AN: 152140Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000931 AC: 234AN: 251382Hom.: 1 AF XY: 0.000898 AC XY: 122AN XY: 135848
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GnomAD4 exome AF: 0.000847 AC: 1238AN: 1461410Hom.: 2 Cov.: 30 AF XY: 0.000857 AC XY: 623AN XY: 727022
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GnomAD4 genome ? AF: 0.000814 AC: 124AN: 152258Hom.: 0 Cov.: 31 AF XY: 0.000833 AC XY: 62AN XY: 74454
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 09, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | GABBR2: BP4, BP7, BS1 - |
Epileptic encephalopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
GABBR2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 31, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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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