Variant 4-47406821-C-T 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 ENST00000295454.8(GABRB1):c.975C>T(p.Ala325=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0832 in 1,613,950 control chromosomes in the GnomAD database, including 6,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 999 hom., cov: 32)

Exomes 𝑓: 0.081 ( 5518 hom. )

Consequence

GABRB1
ENST00000295454.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.472

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=-0.3).

BP6

Variant 4-47406821-C-T is Benign according to our data. Variant chr4-47406821-C-T is described in ClinVar as [Benign]. Clinvar id is 1600634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.472 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 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.975C>T	p.Ala325=	synonymous_variant	8/9	ENST00000295454.8	NP_000803.2
GABRB1	XM_024453976.2 linkuse as main transcript	c.876C>T	p.Ala292=	synonymous_variant	8/9		XP_024309744.1
GABRB1	XM_024453977.2 linkuse as main transcript	c.876C>T	p.Ala292=	synonymous_variant	9/10		XP_024309745.1
GABRB1	XM_017007985.2 linkuse as main transcript	c.324C>T	p.Ala108=	synonymous_variant	4/5		XP_016863474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000295454.8 linkuse as main transcript	c.975C>T	p.Ala325=	synonymous_variant	8/9	1	NM_000812.4	ENSP00000295454	P1	P18505-1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15875

AN:

152004

Hom.:

992

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.0446

Gnomad ASJ

AF:

0.0522

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0733

Gnomad OTH

AF:

0.0903

GnomAD3 exomes

AF:

0.0910

AC:

22873

AN:

251382

Hom.:

1389

AF XY:

0.0934

AC XY:

12683

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.0268

Gnomad ASJ exome

AF:

0.0566

Gnomad EAS exome

AF:

0.146

Gnomad SAS exome

AF:

0.151

Gnomad FIN exome

AF:

0.107

Gnomad NFE exome

AF:

0.0752

Gnomad OTH exome

AF:

0.0771

GnomAD4 exome

AF:

0.0809

AC:

118332

AN:

1461828

Hom.:

5518

Cov.:

AF XY:

0.0826

AC XY:

60056

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.171

Gnomad4 AMR exome

AF:

0.0286

Gnomad4 ASJ exome

AF:

0.0546

Gnomad4 EAS exome

AF:

0.124

Gnomad4 SAS exome

AF:

0.146

Gnomad4 FIN exome

AF:

0.108

Gnomad4 NFE exome

AF:

0.0728

Gnomad4 OTH exome

AF:

0.0875

GnomAD4 genome

AF:

0.105

AC:

15904

AN:

152122

Hom.:

999

Cov.:

AF XY:

0.107

AC XY:

7933

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.170

Gnomad4 AMR

AF:

0.0445

Gnomad4 ASJ

AF:

0.0522

Gnomad4 EAS

AF:

0.143

Gnomad4 SAS

AF:

0.144

Gnomad4 FIN

AF:

0.115

Gnomad4 NFE

AF:

0.0733

Gnomad4 OTH

AF:

0.0898

Alfa

AF:

0.0783

Hom.:

930

Bravo

AF:

0.100

Asia WGS

AF:

0.135

AC:

470

AN:

3478

EpiCase

AF:

0.0696

EpiControl

AF:

0.0721

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

7.4

DANN

Benign

0.67

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