chr5-161869224-G-A

Variant summary

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

The NM_001127644.2(GABRA1):​c.255+3436G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,068 control chromosomes in the GnomAD database, including 3,222 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 0.18 ( 3222 hom., cov: 32)

Consequence

GABRA1
NM_001127644.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.331

Publications

2 publications found
Variant links:
Genes affected
GABRA1 (HGNC:4075): (gamma-aminobutyric acid type A receptor subunit alpha1) 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. Mutations in this gene cause juvenile myoclonic epilepsy and childhood absence epilepsy type 4. Multiple transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]
GABRA1 Gene-Disease associations (from GenCC):
  • developmental and epileptic encephalopathy, 19
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
  • genetic developmental and epileptic encephalopathy
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • epilepsy, idiopathic generalized, susceptibility to, 13
    Inheritance: AD Classification: STRONG Submitted by: G2P
  • Dravet syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • juvenile myoclonic epilepsy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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=-0.97).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GABRA1NM_001127644.2 linkc.255+3436G>A intron_variant Intron 4 of 9 ENST00000393943.10 NP_001121116.1 P14867

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GABRA1ENST00000393943.10 linkc.255+3436G>A intron_variant Intron 4 of 9 1 NM_001127644.2 ENSP00000377517.4 P14867

Frequencies

GnomAD3 genomes
AF:
0.179
AC:
27137
AN:
151952
Hom.:
3221
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.333
Gnomad AMI
AF:
0.0428
Gnomad AMR
AF:
0.0914
Gnomad ASJ
AF:
0.110
Gnomad EAS
AF:
0.276
Gnomad SAS
AF:
0.225
Gnomad FIN
AF:
0.115
Gnomad MID
AF:
0.127
Gnomad NFE
AF:
0.110
Gnomad OTH
AF:
0.153
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.178
AC:
27144
AN:
152068
Hom.:
3222
Cov.:
32
AF XY:
0.178
AC XY:
13257
AN XY:
74312
show subpopulations
African (AFR)
AF:
0.332
AC:
13788
AN:
41468
American (AMR)
AF:
0.0912
AC:
1391
AN:
15256
Ashkenazi Jewish (ASJ)
AF:
0.110
AC:
380
AN:
3466
East Asian (EAS)
AF:
0.276
AC:
1426
AN:
5166
South Asian (SAS)
AF:
0.225
AC:
1085
AN:
4824
European-Finnish (FIN)
AF:
0.115
AC:
1219
AN:
10588
Middle Eastern (MID)
AF:
0.112
AC:
33
AN:
294
European-Non Finnish (NFE)
AF:
0.110
AC:
7463
AN:
67980
Other (OTH)
AF:
0.151
AC:
320
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1061
2122
3184
4245
5306
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
294
588
882
1176
1470
<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:
0.160
Hom.:
405
Bravo
AF:
0.184
Asia WGS
AF:
0.233
AC:
809
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
6.2
DANN
Benign
0.35
PhyloP100
0.33
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: rs7735530; hg19: chr5-161296230; API