Genetic Variant ENST00000513567.5: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

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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