Variant 4-47320202-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000812.4(GABRB1):c.537C>A(p.Ile179=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,579,056 control chromosomes in the GnomAD database, including 29,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2389 hom., cov: 32)

Exomes 𝑓: 0.19 ( 27253 hom. )

Consequence

GABRB1
NM_000812.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0820

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP6

Variant 4-47320202-C-A is Benign according to our data. Variant chr4-47320202-C-A is described in ClinVar as [Benign]. Clinvar id is 1573985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.082 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GABRB1	NM_000812.4 linkuse as main transcript	c.537C>A	p.Ile179=	synonymous_variant	5/9	ENST00000295454.8	NP_000803.2
GABRB1	XM_024453976.2 linkuse as main transcript	c.438C>A	p.Ile146=	synonymous_variant	5/9		XP_024309744.1
GABRB1	XM_024453977.2 linkuse as main transcript	c.438C>A	p.Ile146=	synonymous_variant	6/10		XP_024309745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000295454.8 linkuse as main transcript	c.537C>A	p.Ile179=	synonymous_variant	5/9	1	NM_000812.4	ENSP00000295454	P1	P18505-1
GABRB1	ENST00000510909.1 linkuse as main transcript	c.*205C>A		3_prime_UTR_variant, NMD_transcript_variant	4/5	4		ENSP00000426766		P18505-2

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26172

AN:

152016

Hom.:

2392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.199

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.163

GnomAD3 exomes

AF:

0.170

AC:

42605

AN:

251052

Hom.:

4036

AF XY:

0.170

AC XY:

23073

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.128

Gnomad EAS exome

AF:

0.108

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.202

Gnomad OTH exome

AF:

0.173

GnomAD4 exome

AF:

0.190

AC:

271421

AN:

1426922

Hom.:

27253

Cov.:

AF XY:

0.188

AC XY:

133974

AN XY:

712108

show subpopulations

Gnomad4 AFR exome

AF:

0.122

Gnomad4 AMR exome

AF:

0.131

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.114

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.264

Gnomad4 NFE exome

AF:

0.203

Gnomad4 OTH exome

AF:

0.180

GnomAD4 genome

AF:

0.172

AC:

26169

AN:

152134

Hom.:

2389

Cov.:

AF XY:

0.171

AC XY:

12724

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.128

Gnomad4 EAS

AF:

0.109

Gnomad4 SAS

AF:

0.115

Gnomad4 FIN

AF:

0.255

Gnomad4 NFE

AF:

0.207

Gnomad4 OTH

AF:

0.162

Alfa

AF:

0.190

Hom.:

6505

Bravo

AF:

0.158

Asia WGS

AF:

0.124

AC:

433

AN:

3478

EpiCase

AF:

0.194

EpiControl

AF:

0.196

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 28% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 26. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

6.9

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over