Genetic Variant GABBR1:c.1066-72G>C (chr6-29621889-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001470.4(GABBR1):c.1066-72G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,483,088 control chromosomes in the GnomAD database, including 60,706 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 0.31 ( 7667 hom., cov: 32)

Exomes 𝑓: 0.28 ( 53039 hom. )

Consequence

GABBR1
NM_001470.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.10

Publications

20 publications found

Variant links:

Genes affected

GABBR1 (HGNC:4070): (gamma-aminobutyric acid type B receptor subunit 1) This gene encodes a receptor for gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. This receptor functions as a heterodimer with GABA(B) receptor 2. Defects in this gene may underlie brain disorders such as schizophrenia and epilepsy. Alternative splicing generates multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jan 2016]

GABBR1 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with language delay and variable cognitive abnormalities
Inheritance: AD Classification: MODERATE Submitted by: G2P

GABBR1 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR1	NM_001470.4 link	c.1066-72G>C		intron_variant	Intron 9 of 22	ENST00000377034.9	NP_001461.1	Q9UBS5-1A0A1U9X7R0Q59HG8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR1	ENST00000377034.9 link	c.1066-72G>C		intron_variant	Intron 9 of 22	1	NM_001470.4	ENSP00000366233.4		Q9UBS5-1

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47338

AN:

151980

Hom.:

7650

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.302

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.388

Gnomad FIN

AF:

0.430

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.316

GnomAD4 exome

AF:

0.276

AC:

367437

AN:

1330990

Hom.:

53039

Cov.:

AF XY:

0.278

AC XY:

185804

AN XY:

668912

show subpopulations

African (AFR)

AF:

0.346

AC:

10564

AN:

30552

American (AMR)

AF:

0.282

AC:

12188

AN:

43178

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

4904

AN:

25096

East Asian (EAS)

AF:

0.389

AC:

15107

AN:

38884

South Asian (SAS)

AF:

0.382

AC:

31683

AN:

82996

European-Finnish (FIN)

AF:

0.418

AC:

22070

AN:

52746

Middle Eastern (MID)

AF:

0.264

AC:

1425

AN:

5400

European-Non Finnish (NFE)

AF:

0.255

AC:

253954

AN:

996386

Other (OTH)

AF:

0.279

AC:

15542

AN:

55752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

13825

27651

41476

55302

69127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8320

16640

24960

33280

41600

<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:

0.312

AC:

47391

AN:

152098

Hom.:

7667

Cov.:

AF XY:

0.320

AC XY:

23820

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.346

AC:

14368

AN:

41490

American (AMR)

AF:

0.303

AC:

4634

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

660

AN:

3470

East Asian (EAS)

AF:

0.415

AC:

2145

AN:

5174

South Asian (SAS)

AF:

0.386

AC:

1861

AN:

4822

European-Finnish (FIN)

AF:

0.430

AC:

4542

AN:

10552

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.269

AC:

18291

AN:

67980

Other (OTH)

AF:

0.321

AC:

678

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1681

3363

5044

6726

8407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<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:

0.267

Hom.:

3146

Bravo

AF:

0.302

Asia WGS

AF:

0.460

AC:

1600

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.63

(source)

DANN

Benign

0.63

PhyloP100

-1.1

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