Genetic Variant NM_001470.4:c.*479T>C (chr6-29603064-A-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.*479T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 457,274 control chromosomes in the GnomAD database, including 6,103 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 0.13 ( 1420 hom., cov: 32)

Exomes 𝑓: 0.16 ( 4683 hom. )

Consequence

GABBR1
NM_001470.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.526

Publications

40 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 (REVEL=0.011).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR1	NM_001470.4 link	c.*479T>C		3_prime_UTR_variant	Exon 23 of 23	ENST00000377034.9	NP_001461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR1	ENST00000377034.9 link	c.*479T>C		3_prime_UTR_variant	Exon 23 of 23	1	NM_001470.4	ENSP00000366233.4

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

19061

AN:

152152

Hom.:

1420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.0626

Gnomad MID

AF:

0.210

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.154

GnomAD2 exomes

AF:

0.157

AC:

21658

AN:

137566

AF XY:

0.166

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.0534

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.156

AC:

47607

AN:

305004

Hom.:

4683

Cov.:

AF XY:

0.169

AC XY:

29338

AN XY:

173640

show subpopulations

African (AFR)

AF:

0.115

AC:

991

AN:

8642

American (AMR)

AF:

0.122

AC:

3342

AN:

27288

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

1781

AN:

10798

East Asian (EAS)

AF:

0.237

AC:

2189

AN:

9222

South Asian (SAS)

AF:

0.275

AC:

16434

AN:

59746

European-Finnish (FIN)

AF:

0.0611

AC:

795

AN:

13012

Middle Eastern (MID)

AF:

0.222

AC:

617

AN:

2782

European-Non Finnish (NFE)

AF:

0.122

AC:

19362

AN:

159244

Other (OTH)

AF:

0.147

AC:

2096

AN:

14270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

2835

5671

8506

11342

14177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

200

400

600

800

1000

<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:

0.125

AC:

19070

AN:

152270

Hom.:

1420

Cov.:

AF XY:

0.128

AC XY:

9544

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.108

AC:

4481

AN:

41564

American (AMR)

AF:

0.120

AC:

1832

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.166

AC:

576

AN:

3470

East Asian (EAS)

AF:

0.253

AC:

1303

AN:

5152

South Asian (SAS)

AF:

0.297

AC:

1431

AN:

4822

European-Finnish (FIN)

AF:

0.0626

AC:

665

AN:

10624

Middle Eastern (MID)

AF:

0.195

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.122

AC:

8290

AN:

68020

Other (OTH)

AF:

0.154

AC:

325

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

850

1701

2551

3402

4252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<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:

0.127

Hom.:

5401

Bravo

AF:

0.126

Asia WGS

AF:

0.214

AC:

745

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.70

(source)

DANN

Benign

0.56

PhyloP100

-0.53

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