NM_000807.4:c.187+16258C>T

Variant summary

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

The NM_000807.4(GABRA2):​c.187+16258C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,818 control chromosomes in the GnomAD database, including 4,595 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 0.24 ( 4595 hom., cov: 32)

Consequence

GABRA2
NM_000807.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.242

Publications

22 publications found
Variant links:
Genes affected
GABRA2 (HGNC:4076): (gamma-aminobutyric acid type A receptor subunit alpha2) 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. At least 16 distinct subunits of GABA-A receptors have been identified. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]
GABRA2 Gene-Disease associations (from GenCC):
  • developmental and epileptic encephalopathy, 78
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
  • undetermined early-onset epileptic encephalopathy
    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=-0.92).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GABRA2NM_000807.4 linkc.187+16258C>T intron_variant Intron 3 of 9 ENST00000381620.9 NP_000798.2 P47869-1A0A024R9X6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GABRA2ENST00000381620.9 linkc.187+16258C>T intron_variant Intron 3 of 9 1 NM_000807.4 ENSP00000371033.4 P47869-1

Frequencies

GnomAD3 genomes
AF:
0.239
AC:
36212
AN:
151700
Hom.:
4584
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.279
Gnomad AMI
AF:
0.377
Gnomad AMR
AF:
0.197
Gnomad ASJ
AF:
0.225
Gnomad EAS
AF:
0.0565
Gnomad SAS
AF:
0.0820
Gnomad FIN
AF:
0.177
Gnomad MID
AF:
0.278
Gnomad NFE
AF:
0.257
Gnomad OTH
AF:
0.240
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.239
AC:
36256
AN:
151818
Hom.:
4595
Cov.:
32
AF XY:
0.228
AC XY:
16943
AN XY:
74190
show subpopulations
African (AFR)
AF:
0.280
AC:
11579
AN:
41410
American (AMR)
AF:
0.197
AC:
2996
AN:
15228
Ashkenazi Jewish (ASJ)
AF:
0.225
AC:
781
AN:
3470
East Asian (EAS)
AF:
0.0558
AC:
288
AN:
5160
South Asian (SAS)
AF:
0.0819
AC:
394
AN:
4812
European-Finnish (FIN)
AF:
0.177
AC:
1867
AN:
10538
Middle Eastern (MID)
AF:
0.272
AC:
80
AN:
294
European-Non Finnish (NFE)
AF:
0.257
AC:
17427
AN:
67898
Other (OTH)
AF:
0.239
AC:
502
AN:
2100
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1388
2776
4164
5552
6940
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
362
724
1086
1448
1810
<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:
0.248
Hom.:
18811
Bravo
AF:
0.248
Asia WGS
AF:
0.0890
AC:
311
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
1.1
DANN
Benign
0.46
PhyloP100
-0.24
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: rs9291283; hg19: chr4-46371833; API