Genetic Variant GABRR2:c.1086+68A>G (chr6-89264344-T-C) – 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.1086+68A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 1,507,348 control chromosomes in the GnomAD database, including 555,347 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 0.84 ( 53758 hom., cov: 30)

Exomes 𝑓: 0.86 ( 501589 hom. )

Consequence

GABRR2
NM_002043.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.50

Publications

7 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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR2	NM_002043.5 link	c.1086+68A>G		intron_variant	Intron 8 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.1086+68A>G		intron_variant	Intron 8 of 8	1	NM_002043.5	ENSP00000386029.4		P28476-1
GABRR2	ENST00000602432.1 link	n.917+68A>G		intron_variant	Intron 5 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.839

AC:

127548

AN:

151934

Hom.:

53723

Cov.:

show subpopulations

Gnomad AFR

AF:

0.819

Gnomad AMI

AF:

0.855

Gnomad AMR

AF:

0.800

Gnomad ASJ

AF:

0.815

Gnomad EAS

AF:

0.712

Gnomad SAS

AF:

0.830

Gnomad FIN

AF:

0.850

Gnomad MID

AF:

0.848

Gnomad NFE

AF:

0.870

Gnomad OTH

AF:

0.855

GnomAD4 exome

AF:

0.859

AC:

1164786

AN:

1355296

Hom.:

501589

AF XY:

0.859

AC XY:

572465

AN XY:

666812

show subpopulations

African (AFR)

AF:

0.819

AC:

24275

AN:

29650

American (AMR)

AF:

0.756

AC:

21090

AN:

27910

Ashkenazi Jewish (ASJ)

AF:

0.806

AC:

17777

AN:

22062

East Asian (EAS)

AF:

0.713

AC:

25955

AN:

36428

South Asian (SAS)

AF:

0.826

AC:

61140

AN:

74016

European-Finnish (FIN)

AF:

0.843

AC:

41262

AN:

48938

Middle Eastern (MID)

AF:

0.846

AC:

4533

AN:

5360

European-Non Finnish (NFE)

AF:

0.873

AC:

921083

AN:

1054708

Other (OTH)

AF:

0.848

AC:

47671

AN:

56224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

8072

16143

24215

32286

40358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20660

41320

61980

82640

103300

<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:

0.839

AC:

127634

AN:

152052

Hom.:

53758

Cov.:

AF XY:

0.837

AC XY:

62221

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.818

AC:

33934

AN:

41464

American (AMR)

AF:

0.799

AC:

12223

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.815

AC:

2828

AN:

3472

East Asian (EAS)

AF:

0.712

AC:

3667

AN:

5148

South Asian (SAS)

AF:

0.829

AC:

3984

AN:

4804

European-Finnish (FIN)

AF:

0.850

AC:

8987

AN:

10576

Middle Eastern (MID)

AF:

0.854

AC:

251

AN:

294

European-Non Finnish (NFE)

AF:

0.870

AC:

59175

AN:

67982

Other (OTH)

AF:

0.856

AC:

1805

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1009

2019

3028

4038

5047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.860

Hom.:

88847

Bravo

AF:

0.834

Asia WGS

AF:

0.788

AC:

2740

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

0.29

(source)

DANN

Benign

0.19

PhyloP100

-3.5

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