Genetic Variant GABRR2:c.289-1130A>G (chr6-89270364-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.289-1130A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,056 control chromosomes in the GnomAD database, including 33,104 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 0.66 ( 33093 hom., cov: 31)

Exomes 𝑓: 0.56 ( 11 hom. )

Consequence

GABRR2
NM_002043.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26

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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 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.289-1130A>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.289-1130A>G		intron	N/A	ENSP00000386029.4	P28476-1
	GABRR2	ENST00000602808.1	TSL:3	n.*29A>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.655

AC:

99472

AN:

151876

Hom.:

33043

Cov.:

show subpopulations

Gnomad AFR

AF:

0.779

Gnomad AMI

AF:

0.582

Gnomad AMR

AF:

0.604

Gnomad ASJ

AF:

0.556

Gnomad EAS

AF:

0.708

Gnomad SAS

AF:

0.678

Gnomad FIN

AF:

0.622

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.597

Gnomad OTH

AF:

0.655

GnomAD4 exome

AF:

0.565

AC:

AN:

Hom.:

Cov.:

AF XY:

0.550

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.554

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.655

AC:

99574

AN:

151994

Hom.:

33093

Cov.:

AF XY:

0.656

AC XY:

48747

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.779

AC:

32297

AN:

41452

American (AMR)

AF:

0.604

AC:

9223

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.556

AC:

1932

AN:

3472

East Asian (EAS)

AF:

0.708

AC:

3645

AN:

5148

South Asian (SAS)

AF:

0.677

AC:

3261

AN:

4814

European-Finnish (FIN)

AF:

0.622

AC:

6573

AN:

10570

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.597

AC:

40555

AN:

67946

Other (OTH)

AF:

0.657

AC:

1387

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1749

3497

5246

6994

8743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<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:

0.623

Hom.:

44792

Bravo

AF:

0.657

Asia WGS

AF:

0.722

AC:

2513

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.42

(source)

DANN

Benign

0.49

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over