Menu
GeneBe

rs3205936

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005458.8(GABBR2):​c.1587C>T​(p.Leu529=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00914 in 1,605,760 control chromosomes in the GnomAD database, including 1,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 651 hom., cov: 32)
Exomes 𝑓: 0.0049 ( 537 hom. )

Consequence

GABBR2
NM_005458.8 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.363
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-98385715-G-A is Benign according to our data. Variant chr9-98385715-G-A is described in ClinVar as [Benign]. Clinvar id is 462125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.363 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GABBR2NM_005458.8 linkuse as main transcriptc.1587C>T p.Leu529= synonymous_variant 11/19 ENST00000259455.4
GABBR2XM_017015331.3 linkuse as main transcriptc.1293C>T p.Leu431= synonymous_variant 10/18
GABBR2XM_005252316.6 linkuse as main transcriptc.813C>T p.Leu271= synonymous_variant 9/17
GABBR2XM_017015332.3 linkuse as main transcriptc.813C>T p.Leu271= synonymous_variant 8/16

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GABBR2ENST00000259455.4 linkuse as main transcriptc.1587C>T p.Leu529= synonymous_variant 11/191 NM_005458.8 P1
GABBR2ENST00000634314.1 linkuse as main transcriptn.92C>T non_coding_transcript_exon_variant 2/43
GABBR2ENST00000637410.1 linkuse as main transcriptn.1365C>T non_coding_transcript_exon_variant 11/195

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0495
AC:
7526
AN:
152130
Hom.:
652
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.171
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0213
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000828
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0222
Gnomad NFE
AF:
0.000514
Gnomad OTH
AF:
0.0354
GnomAD3 exomes
AF:
0.0124
AC:
3126
AN:
251432
Hom.:
246
AF XY:
0.00908
AC XY:
1234
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.170
Gnomad AMR exome
AF:
0.00758
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000484
Gnomad OTH exome
AF:
0.00668
GnomAD4 exome
AF:
0.00491
AC:
7142
AN:
1453512
Hom.:
537
Cov.:
27
AF XY:
0.00414
AC XY:
2998
AN XY:
723668
show subpopulations
Gnomad4 AFR exome
AF:
0.174
Gnomad4 AMR exome
AF:
0.00890
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000360
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000188
Gnomad4 OTH exome
AF:
0.0115
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0495
AC:
7529
AN:
152248
Hom.:
651
Cov.:
32
AF XY:
0.0472
AC XY:
3511
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.171
Gnomad4 AMR
AF:
0.0213
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000829
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000515
Gnomad4 OTH
AF:
0.0350
Alfa
AF:
0.0262
Hom.:
181
Bravo
AF:
0.0577
Asia WGS
AF:
0.00953
AC:
34
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.000652

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Epileptic encephalopathy Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJul 17, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
CADD
Benign
4.3
DANN
Benign
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3205936; hg19: chr9-101147997; API