Genetic Variant GABRR2:c.513-33G>A (chr6-89268129-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002043.5(GABRR2):c.513-33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,536,946 control chromosomes in the GnomAD database, including 14,428 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 0.12 ( 1290 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13138 hom. )

Consequence

GABRR2
NM_002043.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.907

Publications

5 publications found

Variant links:

Genes affected

GABRR2 (HGNC:4091): (gamma-aminobutyric acid type A receptor subunit rho2) Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. The protein encoded by this gene is a member of the rho subunit family and is a component of the GABA type A receptor complex. This gene exists on chromosome 6q next to the gene encoding the rho 1 subunit of the GABA type A receptor, in a region thought to be associated with susceptibility for psychiatric disorders and epilepsy. Polymorphisms in this gene may also be associated with alcohol dependence, and general cognitive ability. [provided by RefSeq, Apr 2016]

GABRR2 links:

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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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR2	NM_002043.5 link	c.513-33G>A		intron_variant	Intron 4 of 8	ENST00000402938.4	NP_002034.3	P28476-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4 link	c.513-33G>A		intron_variant	Intron 4 of 8	1	NM_002043.5	ENSP00000386029.4		P28476-1
GABRR2	ENST00000602432.1 link	n.344-33G>A		intron_variant	Intron 1 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18436

AN:

152068

Hom.:

1290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0921

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.0884

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.133

GnomAD2 exomes

AF:

0.146

AC:

28196

AN:

193676

AF XY:

0.145

show subpopulations

Gnomad AFR exome

AF:

0.0955

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.0934

Gnomad EAS exome

AF:

0.415

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.130

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.128

AC:

176608

AN:

1384758

Hom.:

13138

Cov.:

AF XY:

0.127

AC XY:

87558

AN XY:

687986

show subpopulations

African (AFR)

AF:

0.0934

AC:

2963

AN:

31734

American (AMR)

AF:

0.133

AC:

5163

AN:

38904

Ashkenazi Jewish (ASJ)

AF:

0.0897

AC:

2262

AN:

25208

East Asian (EAS)

AF:

0.418

AC:

15675

AN:

37468

South Asian (SAS)

AF:

0.118

AC:

9516

AN:

80588

European-Finnish (FIN)

AF:

0.123

AC:

6285

AN:

51272

Middle Eastern (MID)

AF:

0.123

AC:

648

AN:

5266

European-Non Finnish (NFE)

AF:

0.120

AC:

126538

AN:

1056588

Other (OTH)

AF:

0.131

AC:

7558

AN:

57730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

7949

15899

23848

31798

39747

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4600

9200

13800

18400

23000

<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:

0.121

AC:

18434

AN:

152188

Hom.:

1290

Cov.:

AF XY:

0.123

AC XY:

9128

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0919

AC:

3817

AN:

41522

American (AMR)

AF:

0.124

AC:

1893

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0884

AC:

307

AN:

3472

East Asian (EAS)

AF:

0.395

AC:

2042

AN:

5176

South Asian (SAS)

AF:

0.129

AC:

620

AN:

4824

European-Finnish (FIN)

AF:

0.118

AC:

1247

AN:

10578

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.120

AC:

8157

AN:

67994

Other (OTH)

AF:

0.132

AC:

280

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

836

1671

2507

3342

4178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

214

428

642

856

1070

<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:

0.122

Hom.:

1193

Bravo

AF:

0.122

Asia WGS

AF:

0.247

AC:

854

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.3

(source)

DANN

Benign

0.66

PhyloP100

-0.91

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