4-47320173-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000812.4(GABRB1):c.508T>C(p.Leu170Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.986 in 1,607,758 control chromosomes in the GnomAD database, including 781,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L170L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.97 ( 71759 hom., cov: 31)

Exomes 𝑓: 0.99 ( 709777 hom. )

Consequence

GABRB1
NM_000812.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.23

Publications

16 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 4-47320173-T-C is Benign according to our data. Variant chr4-47320173-T-C is described in ClinVar as [Benign]. Clinvar id is 1642812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB1	NM_000812.4 link	c.508T>C	p.Leu170Leu	synonymous_variant	Exon 5 of 9	ENST00000295454.8	NP_000803.2	P18505-1X5DNL6
GABRB1	XM_024453976.2 link	c.409T>C	p.Leu137Leu	synonymous_variant	Exon 5 of 9		XP_024309744.1
GABRB1	XM_024453977.2 link	c.409T>C	p.Leu137Leu	synonymous_variant	Exon 6 of 10		XP_024309745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GABRB1	ENST00000295454.8 link	c.508T>C	p.Leu170Leu	synonymous_variant	Exon 5 of 9	1	NM_000812.4	ENSP00000295454.3	P18505-1
GABRB1	ENST00000510909.1 link	n.*176T>C		non_coding_transcript_exon_variant	Exon 4 of 5	4		ENSP00000426766.1	P18505-2
GABRB1	ENST00000510909.1 link	n.*176T>C		3_prime_UTR_variant	Exon 4 of 5	4		ENSP00000426766.1	P18505-2

Frequencies

GnomAD3 genomes

AF:

0.970

AC:

147638

AN:

152190

Hom.:

71710

Cov.:

show subpopulations

Gnomad AFR

AF:

0.919

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.985

Gnomad ASJ

AF:

0.976

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.996

Gnomad FIN

AF:

0.998

Gnomad MID

AF:

0.962

Gnomad NFE

AF:

0.989

Gnomad OTH

AF:

0.976

GnomAD2 exomes

AF:

0.986

AC:

247796

AN:

251420

AF XY:

0.987

show subpopulations

Gnomad AFR exome

AF:

0.917

Gnomad AMR exome

AF:

0.988

Gnomad ASJ exome

AF:

0.976

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.998

Gnomad NFE exome

AF:

0.988

Gnomad OTH exome

AF:

0.985

GnomAD4 exome

AF:

0.987

AC:

1437241

AN:

1455450

Hom.:

709777

Cov.:

AF XY:

0.988

AC XY:

715692

AN XY:

724532

show subpopulations

African (AFR)

AF:

0.916

AC:

30531

AN:

33328

American (AMR)

AF:

0.988

AC:

44169

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.977

AC:

25487

AN:

26100

East Asian (EAS)

AF:

1.00

AC:

39662

AN:

39664

South Asian (SAS)

AF:

0.996

AC:

85838

AN:

86170

European-Finnish (FIN)

AF:

0.998

AC:

53311

AN:

53416

Middle Eastern (MID)

AF:

0.952

AC:

5486

AN:

5764

European-Non Finnish (NFE)

AF:

0.989

AC:

1093593

AN:

1106044

Other (OTH)

AF:

0.982

AC:

59164

AN:

60242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

784

1568

2351

3135

3919

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.970

AC:

147744

AN:

152308

Hom.:

71759

Cov.:

AF XY:

0.971

AC XY:

72303

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.919

AC:

38192

AN:

41552

American (AMR)

AF:

0.985

AC:

15062

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.976

AC:

3388

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5177

AN:

5180

South Asian (SAS)

AF:

0.996

AC:

4810

AN:

4828

European-Finnish (FIN)

AF:

0.998

AC:

10599

AN:

10622

Middle Eastern (MID)

AF:

0.959

AC:

282

AN:

294

European-Non Finnish (NFE)

AF:

0.989

AC:

67259

AN:

68040

Other (OTH)

AF:

0.976

AC:

2063

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

203

405

608

810

1013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.978

Hom.:

32115

Bravo

AF:

0.966

Asia WGS

AF:

0.994

AC:

3456

AN:

3478

EpiCase

AF:

0.987

EpiControl

AF:

0.986

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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 100% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 93. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

2.2

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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4-47320173-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over