dbSNP rs55941866: GABBR1:c.2713-84C>T (chr6-29603800-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . 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: STRONG, MODERATE Submitted by: G2P, PanelApp Australia

GABBR1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001470.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001470.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GABBR1	NM_001470.4	MANE Select	c.2713-84C>T	intron	N/A	NP_001461.1	A0A1U9X7R0
GABBR1	NM_021904.4		c.2527-84C>T	intron	N/A	NP_068704.2	Q9UBS5-3
GABBR1	NM_021903.3		c.2362-84C>T	intron	N/A	NP_068703.1	Q5SUJ9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GABBR1	ENST00000377034.9	TSL:1 MANE Select	c.2713-84C>T	intron	N/A	ENSP00000366233.4	Q9UBS5-1
GABBR1	ENST00000377012.9	TSL:1	c.2362-84C>T	intron	N/A	ENSP00000366211.4	Q9UBS5-2
GABBR1	ENST00000476670.3	TSL:4	c.2728-84C>T	intron	N/A	ENSP00000417332.2	C9J342

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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