Genetic Variant GABRR2:c.889+87C>G (chr6-89265526-G-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.889+87C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,433,578 control chromosomes in the GnomAD database, including 467,463 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 0.80 ( 48206 hom., cov: 30)

Exomes 𝑓: 0.81 ( 419257 hom. )

Consequence

GABRR2
NM_002043.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.817

Publications

3 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 = 0.809 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR2	NM_002043.5	MANE Select	c.889+87C>G		intron	N/A	NP_002034.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR2	ENST00000402938.4	TSL:1 MANE Select	c.889+87C>G		intron	N/A	ENSP00000386029.4
	GABRR2	ENST00000602432.1	TSL:2	n.720+87C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.795

AC:

120774

AN:

151876

Hom.:

48169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.789

Gnomad AMI

AF:

0.752

Gnomad AMR

AF:

0.754

Gnomad ASJ

AF:

0.794

Gnomad EAS

AF:

0.694

Gnomad SAS

AF:

0.796

Gnomad FIN

AF:

0.805

Gnomad MID

AF:

0.829

Gnomad NFE

AF:

0.814

Gnomad OTH

AF:

0.815

GnomAD4 exome

AF:

0.808

AC:

1035888

AN:

1281582

Hom.:

419257

AF XY:

0.808

AC XY:

509898

AN XY:

631306

show subpopulations

African (AFR)

AF:

0.793

AC:

22605

AN:

28516

American (AMR)

AF:

0.717

AC:

19398

AN:

27054

Ashkenazi Jewish (ASJ)

AF:

0.787

AC:

15512

AN:

19700

East Asian (EAS)

AF:

0.700

AC:

26272

AN:

37524

South Asian (SAS)

AF:

0.794

AC:

51179

AN:

64462

European-Finnish (FIN)

AF:

0.797

AC:

38205

AN:

47914

Middle Eastern (MID)

AF:

0.824

AC:

3878

AN:

4704

European-Non Finnish (NFE)

AF:

0.817

AC:

815824

AN:

998240

Other (OTH)

AF:

0.804

AC:

43015

AN:

53468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

9196

18392

27589

36785

45981

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19132

38264

57396

76528

95660

<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:

0.795

AC:

120860

AN:

151996

Hom.:

48206

Cov.:

AF XY:

0.795

AC XY:

59037

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.789

AC:

32681

AN:

41434

American (AMR)

AF:

0.754

AC:

11514

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.794

AC:

2756

AN:

3470

East Asian (EAS)

AF:

0.694

AC:

3583

AN:

5164

South Asian (SAS)

AF:

0.795

AC:

3828

AN:

4814

European-Finnish (FIN)

AF:

0.805

AC:

8489

AN:

10546

Middle Eastern (MID)

AF:

0.837

AC:

246

AN:

294

European-Non Finnish (NFE)

AF:

0.814

AC:

55359

AN:

67988

Other (OTH)

AF:

0.816

AC:

1721

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1251

2502

3752

5003

6254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<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:

0.800

Hom.:

5698

Bravo

AF:

0.790

Asia WGS

AF:

0.765

AC:

2662

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

0.54

(source)

DANN

Benign

0.30

PhyloP100

-0.82

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