15-27025278-T-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033223.5(GABRG3):​c.203-1476T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 151,998 control chromosomes in the GnomAD database, including 33,550 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.66 ( 33550 hom., cov: 32)

Consequence

GABRG3
NM_033223.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.962

Publications

1 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GABRG3NM_033223.5 linkc.203-1476T>A intron_variant Intron 2 of 9 ENST00000615808.5 NP_150092.2 Q99928-1
GABRG3NM_001270873.2 linkc.203-1476T>A intron_variant Intron 2 of 5 NP_001257802.1 Q99928-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GABRG3ENST00000615808.5 linkc.203-1476T>A intron_variant Intron 2 of 9 1 NM_033223.5 ENSP00000479113.1 Q99928-1
GABRG3ENST00000555083.5 linkc.203-1476T>A intron_variant Intron 2 of 5 2 ENSP00000452244.1 Q99928-2
GABRG3ENST00000553440.1 linkn.295-1476T>A intron_variant Intron 2 of 2 3

Frequencies

GnomAD3 genomes
AF:
0.663
AC:
100739
AN:
151880
Hom.:
33526
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.712
Gnomad AMI
AF:
0.729
Gnomad AMR
AF:
0.654
Gnomad ASJ
AF:
0.705
Gnomad EAS
AF:
0.690
Gnomad SAS
AF:
0.661
Gnomad FIN
AF:
0.657
Gnomad MID
AF:
0.630
Gnomad NFE
AF:
0.633
Gnomad OTH
AF:
0.653
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.663
AC:
100818
AN:
151998
Hom.:
33550
Cov.:
32
AF XY:
0.664
AC XY:
49362
AN XY:
74292
show subpopulations
African (AFR)
AF:
0.712
AC:
29485
AN:
41438
American (AMR)
AF:
0.654
AC:
9994
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.705
AC:
2446
AN:
3470
East Asian (EAS)
AF:
0.689
AC:
3539
AN:
5138
South Asian (SAS)
AF:
0.660
AC:
3180
AN:
4820
European-Finnish (FIN)
AF:
0.657
AC:
6944
AN:
10568
Middle Eastern (MID)
AF:
0.639
AC:
188
AN:
294
European-Non Finnish (NFE)
AF:
0.633
AC:
42993
AN:
67966
Other (OTH)
AF:
0.655
AC:
1384
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1753
3505
5258
7010
8763
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
804
1608
2412
3216
4020
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.646
Hom.:
3939
Bravo
AF:
0.666
Asia WGS
AF:
0.676
AC:
2351
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
6.8
DANN
Benign
0.54
PhyloP100
0.96
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs6606858; hg19: chr15-27270425; API