Genetic Variant GABRR2:c.114-2851C>T (chr6-89302716-G-A) – 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.114-2851C>T variant causes a intron change. The variant allele was found at a frequency of 0.533 in 1,355,220 control chromosomes in the GnomAD database, including 200,823 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 0.60 ( 29030 hom., cov: 32)

Exomes 𝑓: 0.52 ( 171793 hom. )

Consequence

GABRR2
NM_002043.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.94

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:

TUBB3P1 (HGNC:42339): (tubulin beta 3 class III pseudogene 1)

TUBB3P1 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=-0.6).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GABRR2	NM_002043.5 link	c.114-2851C>T	intron_variant	Intron 1 of 8	ENST00000402938.4	NP_002034.3	P28476-1
TUBB3P1		n.89302716G>A	intragenic_variant
GABRR2	XM_047418599.1 link	c.189-2851C>T	intron_variant	Intron 1 of 9		XP_047274555.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GABRR2	ENST00000402938.4 link	c.114-2851C>T	intron_variant	Intron 1 of 8	1	NM_002043.5	ENSP00000386029.4	P28476-1
TUBB3P1	ENST00000405796.1 link	n.934G>A	non_coding_transcript_exon_variant	Exon 1 of 1	6
GABRR2	ENST00000602808.1 link	n.248-2851C>T	intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.604

AC:

91775

AN:

151958

Hom.:

28985

Cov.:

show subpopulations

Gnomad AFR

AF:

0.779

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.531

Gnomad ASJ

AF:

0.578

Gnomad EAS

AF:

0.724

Gnomad SAS

AF:

0.780

Gnomad FIN

AF:

0.573

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.500

Gnomad OTH

AF:

0.588

GnomAD4 exome

AF:

0.524

AC:

630559

AN:

1203142

Hom.:

171793

Cov.:

AF XY:

0.532

AC XY:

321423

AN XY:

603944

show subpopulations

African (AFR)

AF:

0.776

AC:

20839

AN:

26858

American (AMR)

AF:

0.522

AC:

21253

AN:

40722

Ashkenazi Jewish (ASJ)

AF:

0.556

AC:

11558

AN:

20802

East Asian (EAS)

AF:

0.719

AC:

19343

AN:

26892

South Asian (SAS)

AF:

0.766

AC:

62897

AN:

82088

European-Finnish (FIN)

AF:

0.554

AC:

24199

AN:

43650

Middle Eastern (MID)

AF:

0.575

AC:

2432

AN:

4230

European-Non Finnish (NFE)

AF:

0.485

AC:

441681

AN:

910346

Other (OTH)

AF:

0.554

AC:

26357

AN:

47554

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

12146

24293

36439

48586

60732

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.604

AC:

91879

AN:

152078

Hom.:

29030

Cov.:

AF XY:

0.612

AC XY:

45460

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.779

AC:

32367

AN:

41540

American (AMR)

AF:

0.531

AC:

8113

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.578

AC:

2003

AN:

3466

East Asian (EAS)

AF:

0.724

AC:

3722

AN:

5144

South Asian (SAS)

AF:

0.779

AC:

3756

AN:

4820

European-Finnish (FIN)

AF:

0.573

AC:

6048

AN:

10554

Middle Eastern (MID)

AF:

0.599

AC:

176

AN:

294

European-Non Finnish (NFE)

AF:

0.500

AC:

33944

AN:

67944

Other (OTH)

AF:

0.593

AC:

1253

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1758

3516

5275

7033

8791

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.549

Hom.:

2980

Bravo

AF:

0.603

Asia WGS

AF:

0.764

AC:

2659

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.8

(source)

DANN

Benign

0.65

PhyloP100

3.9

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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chr6-89302716-G-A

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