4-47406692-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000812.4(GABRB1):c.846A>G(p.Thr282Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,613,724 control chromosomes in the GnomAD database, including 74,786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6283 hom., cov: 32)

Exomes 𝑓: 0.30 ( 68503 hom. )

Consequence

GABRB1
NM_000812.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.03

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 4-47406692-A-G is Benign according to our data. Variant chr4-47406692-A-G is described in ClinVar as [Benign]. Clinvar id is 1280390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB1	NM_000812.4 link	c.846A>G	p.Thr282Thr	synonymous_variant	Exon 8 of 9	ENST00000295454.8	NP_000803.2	P18505-1X5DNL6
GABRB1	XM_024453976.2 link	c.747A>G	p.Thr249Thr	synonymous_variant	Exon 8 of 9		XP_024309744.1
GABRB1	XM_024453977.2 link	c.747A>G	p.Thr249Thr	synonymous_variant	Exon 9 of 10		XP_024309745.1
GABRB1	XM_017007985.2 link	c.195A>G	p.Thr65Thr	synonymous_variant	Exon 4 of 5		XP_016863474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000295454.8 link	c.846A>G	p.Thr282Thr	synonymous_variant	Exon 8 of 9	1	NM_000812.4	ENSP00000295454.3		P18505-1

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42252

AN:

151994

Hom.:

6277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.334

Gnomad EAS

AF:

0.0154

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.280

GnomAD3 exomes

AF:

0.255

AC:

64042

AN:

251168

Hom.:

9420

AF XY:

0.261

AC XY:

35407

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.272

Gnomad AMR exome

AF:

0.153

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.00810

Gnomad SAS exome

AF:

0.203

Gnomad FIN exome

AF:

0.273

Gnomad NFE exome

AF:

0.326

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.299

AC:

436528

AN:

1461612

Hom.:

68503

Cov.:

AF XY:

0.297

AC XY:

216055

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.276

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.338

Gnomad4 EAS exome

AF:

0.0255

Gnomad4 SAS exome

AF:

0.209

Gnomad4 FIN exome

AF:

0.270

Gnomad4 NFE exome

AF:

0.322

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.278

AC:

42284

AN:

152112

Hom.:

6283

Cov.:

AF XY:

0.273

AC XY:

20325

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.268

Gnomad4 AMR

AF:

0.220

Gnomad4 ASJ

AF:

0.334

Gnomad4 EAS

AF:

0.0154

Gnomad4 SAS

AF:

0.203

Gnomad4 FIN

AF:

0.286

Gnomad4 NFE

AF:

0.318

Gnomad4 OTH

AF:

0.282

Alfa

AF:

0.308

Hom.:

12494

Bravo

AF:

0.274

Asia WGS

AF:

0.128

AC:

445

AN:

3478

EpiCase

AF:

0.337

EpiControl

AF:

0.338

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 29% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 27. Only high quality variants are reported. -

Developmental and epileptic encephalopathy, 45

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.012

DANN

Benign

0.29

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

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