Genetic Variant GABBR1:p.Ser515Ser (chr6-29613264-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001470.4(GABBR1):c.1545T>C(p.Ser515Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0984 in 1,610,224 control chromosomes in the GnomAD database, including 8,517 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 0.098 ( 861 hom., cov: 32)

Exomes 𝑓: 0.098 ( 7656 hom. )

Consequence

GABBR1
NM_001470.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.00

Publications

19 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP7

Synonymous conserved (PhyloP=1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR1	NM_001470.4 link	c.1545T>C	p.Ser515Ser	synonymous_variant	Exon 12 of 23	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.1545T>C	p.Ser515Ser	synonymous_variant	Exon 12 of 23	1	NM_001470.4	ENSP00000366233.4		Q9UBS5-1

Frequencies

GnomAD3 genomes

AF:

0.0980

AC:

14908

AN:

152172

Hom.:

858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0897

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.0999

Gnomad ASJ

AF:

0.0862

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.0439

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.120

GnomAD2 exomes

AF:

0.0987

AC:

24313

AN:

246452

AF XY:

0.102

show subpopulations

Gnomad AFR exome

AF:

0.0972

Gnomad AMR exome

AF:

0.0715

Gnomad ASJ exome

AF:

0.0875

Gnomad EAS exome

AF:

0.147

Gnomad FIN exome

AF:

0.0468

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.108

GnomAD4 exome

AF:

0.0985

AC:

143563

AN:

1457934

Hom.:

7656

Cov.:

AF XY:

0.100

AC XY:

72749

AN XY:

725392

show subpopulations

African (AFR)

AF:

0.0921

AC:

3080

AN:

33428

American (AMR)

AF:

0.0754

AC:

3373

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0906

AC:

2365

AN:

26112

East Asian (EAS)

AF:

0.0836

AC:

3317

AN:

39684

South Asian (SAS)

AF:

0.138

AC:

11861

AN:

86162

European-Finnish (FIN)

AF:

0.0501

AC:

2622

AN:

52312

Middle Eastern (MID)

AF:

0.163

AC:

940

AN:

5760

European-Non Finnish (NFE)

AF:

0.0988

AC:

109587

AN:

1109478

Other (OTH)

AF:

0.106

AC:

6418

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

6387

12774

19162

25549

31936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3982

7964

11946

15928

19910

<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:

0.0979

AC:

14915

AN:

152290

Hom.:

861

Cov.:

AF XY:

0.0988

AC XY:

7359

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0896

AC:

3724

AN:

41546

American (AMR)

AF:

0.0997

AC:

1525

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0862

AC:

299

AN:

3468

East Asian (EAS)

AF:

0.127

AC:

656

AN:

5182

South Asian (SAS)

AF:

0.158

AC:

765

AN:

4832

European-Finnish (FIN)

AF:

0.0439

AC:

466

AN:

10622

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.104

AC:

7046

AN:

68020

Other (OTH)

AF:

0.119

AC:

251

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

693

1385

2078

2770

3463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<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:

0.0994

Hom.:

2321

Bravo

AF:

0.103

Asia WGS

AF:

0.109

AC:

380

AN:

3478

EpiCase

AF:

0.116

EpiControl

AF:

0.110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.9

(source)

DANN

Benign

0.70

PhyloP100

1.0

Mutation Taster

=92/8

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