dbSNP rs55941866: GABBR1:c.2713-84C>T (chr6-29603800-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_001470.4(GABBR1):c.2713-84C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 1,066,380 control chromosomes in the GnomAD database, including 968 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 0.036 ( 198 hom., cov: 31)

Exomes 𝑓: 0.030 ( 770 hom. )

Consequence

GABBR1
NM_001470.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0490

Publications

0 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:

Genome browser will be placed here

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=-0.74).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR1	NM_001470.4 link	c.2713-84C>T		intron_variant	Intron 22 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.2713-84C>T		intron_variant	Intron 22 of 22	1	NM_001470.4	ENSP00000366233.4		Q9UBS5-1

Frequencies

GnomAD3 genomes

AF:

0.0362

AC:

5499

AN:

152036

Hom.:

199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0168

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0935

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.0476

Gnomad SAS

AF:

0.0966

Gnomad FIN

AF:

0.0191

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0281

Gnomad OTH

AF:

0.0374

GnomAD4 exome

AF:

0.0299

AC:

27347

AN:

914226

Hom.:

770

AF XY:

0.0320

AC XY:

14278

AN XY:

446460

show subpopulations

African (AFR)

AF:

0.0148

AC:

316

AN:

21382

American (AMR)

AF:

0.0979

AC:

1292

AN:

13196

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

1951

AN:

15022

East Asian (EAS)

AF:

0.0456

AC:

1415

AN:

31016

South Asian (SAS)

AF:

0.107

AC:

3671

AN:

34288

European-Finnish (FIN)

AF:

0.0234

AC:

691

AN:

29470

Middle Eastern (MID)

AF:

0.0732

AC:

320

AN:

4374

European-Non Finnish (NFE)

AF:

0.0221

AC:

16038

AN:

725210

Other (OTH)

AF:

0.0411

AC:

1653

AN:

40268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1344

2687

4031

5374

6718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

648

1296

1944

2592

3240

<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:

0.0362

AC:

5504

AN:

152154

Hom.:

198

Cov.:

AF XY:

0.0379

AC XY:

2817

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0168

AC:

696

AN:

41502

American (AMR)

AF:

0.0934

AC:

1429

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

459

AN:

3468

East Asian (EAS)

AF:

0.0477

AC:

246

AN:

5160

South Asian (SAS)

AF:

0.0981

AC:

472

AN:

4812

European-Finnish (FIN)

AF:

0.0191

AC:

203

AN:

10610

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0281

AC:

1910

AN:

67990

Other (OTH)

AF:

0.0370

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

256

511

767

1022

1278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0299

Hom.:

Bravo

AF:

0.0399

Asia WGS

AF:

0.0710

AC:

249

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.1

(source)

DANN

Benign

0.82

PhyloP100

0.049

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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