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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002043.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR2	NM_002043.5	MANE Select	c.1086+68A>G		intron	N/A	NP_002034.3	P28476-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR2	ENST00000402938.4	TSL:1 MANE Select	c.1086+68A>G		intron	N/A	ENSP00000386029.4	P28476-1
	GABRR2	ENST00000602432.1	TSL:2	n.917+68A>G		intron	N/A

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over