dbSNP rs3762607: GABRB1:c.-20+395A>G (chr4-46994321-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 ENST00000513567.5(GABRB1):c.-20+395A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0854 in 151,946 control chromosomes in the GnomAD database, including 637 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 0.085 ( 637 hom., cov: 31)

Exomes 𝑓: 0.026 ( 0 hom. )

Consequence

GABRB1
ENST00000513567.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.231

Publications

5 publications found

Variant links:

Genes affected

GABRB1 (HGNC:4081): (gamma-aminobutyric acid type A receptor subunit beta1) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes GABA A receptor, beta 1 subunit. It is mapped to chromosome 4p12 in a cluster comprised of genes encoding alpha 4, alpha 2 and gamma 1 subunits of the GABA A receptor. Alteration of this gene is implicated in the pathogenetics of schizophrenia. [provided by RefSeq, Jul 2008]

GABRB1 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 45
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

GABRB1 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=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB1	XM_024453976.2 link	c.-20+361A>G		intron_variant	Intron 1 of 8		XP_024309744.1
GABRB1	XM_024453977.2 link	c.-57-56A>G		intron_variant	Intron 1 of 9		XP_024309745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000513567.5 link	c.-20+395A>G		intron_variant	Intron 1 of 3	4		ENSP00000426753.1		D6REM0

Frequencies

GnomAD3 genomes

AF:

0.0853

AC:

12948

AN:

151750

Hom.:

636

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0942

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0734

Gnomad ASJ

AF:

0.0919

Gnomad EAS

AF:

0.0982

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.0838

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0749

Gnomad OTH

AF:

0.0815

GnomAD4 exome

AF:

0.0256

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0370

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0854

AC:

12967

AN:

151868

Hom.:

637

Cov.:

AF XY:

0.0871

AC XY:

6466

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.0946

AC:

3915

AN:

41406

American (AMR)

AF:

0.0733

AC:

1119

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0919

AC:

319

AN:

3470

East Asian (EAS)

AF:

0.0987

AC:

506

AN:

5128

South Asian (SAS)

AF:

0.189

AC:

907

AN:

4798

European-Finnish (FIN)

AF:

0.0838

AC:

884

AN:

10544

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0749

AC:

5091

AN:

67934

Other (OTH)

AF:

0.0825

AC:

174

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

606

1212

1818

2424

3030

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<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:

0.0842

Hom.:

231

Bravo

AF:

0.0806

Asia WGS

AF:

0.153

AC:

533

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.4

(source)

DANN

Benign

0.60

PhyloP100

-0.23

Mutation Taster

=298/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over