dbSNP rs11503014: GABRA2:c.-10-132G>C (chr4-46388848-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000807.4(GABRA2):c.-10-132G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,437,656 control chromosomes in the GnomAD database, including 57,351 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 0.27 ( 5579 hom., cov: 32)

Exomes 𝑓: 0.28 ( 51772 hom. )

Consequence

GABRA2
NM_000807.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0350

Publications

29 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

GABRA2 links:

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=-0.94).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA2	NM_000807.4 link	c.-10-132G>C		intron_variant	Intron 1 of 9	ENST00000381620.9	NP_000798.2	P47869-1A0A024R9X6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000381620.9 link	c.-10-132G>C		intron_variant	Intron 1 of 9	1	NM_000807.4	ENSP00000371033.4		P47869-1

Frequencies

GnomAD3 genomes

AF:

0.269

AC:

40824

AN:

151984

Hom.:

5569

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.0892

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.283

GnomAD4 exome

AF:

0.284

AC:

364587

AN:

1285554

Hom.:

51772

Cov.:

AF XY:

0.282

AC XY:

176160

AN XY:

625176

show subpopulations

African (AFR)

AF:

0.298

AC:

8277

AN:

27786

American (AMR)

AF:

0.239

AC:

4766

AN:

19942

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

4602

AN:

19082

East Asian (EAS)

AF:

0.129

AC:

4211

AN:

32748

South Asian (SAS)

AF:

0.181

AC:

10409

AN:

57472

European-Finnish (FIN)

AF:

0.263

AC:

11892

AN:

45280

Middle Eastern (MID)

AF:

0.275

AC:

1130

AN:

4116

European-Non Finnish (NFE)

AF:

0.297

AC:

305171

AN:

1026198

Other (OTH)

AF:

0.267

AC:

14129

AN:

52930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

12657

25314

37971

50628

63285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10428

20856

31284

41712

52140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.269

AC:

40865

AN:

152102

Hom.:

5579

Cov.:

AF XY:

0.260

AC XY:

19298

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.286

AC:

11865

AN:

41480

American (AMR)

AF:

0.233

AC:

3557

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

764

AN:

3468

East Asian (EAS)

AF:

0.0883

AC:

456

AN:

5166

South Asian (SAS)

AF:

0.158

AC:

764

AN:

4826

European-Finnish (FIN)

AF:

0.246

AC:

2596

AN:

10572

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.293

AC:

19889

AN:

67980

Other (OTH)

AF:

0.283

AC:

598

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1527

3054

4582

6109

7636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.270

Hom.:

677

Bravo

AF:

0.270

Asia WGS

AF:

0.141

AC:

490

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

4.1

(source)

DANN

Benign

0.58

PhyloP100

-0.035

PromoterAI

0.020

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over