GeneBe

NM_000812.4:c.537C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_000812.4(GABRB1):​c.537C>T​(p.Ile179Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,433,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I179I) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GABRB1
NM_000812.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0820

Publications

13 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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP7
Synonymous conserved (PhyloP=0.082 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GABRB1NM_000812.4 linkc.537C>T p.Ile179Ile synonymous_variant Exon 5 of 9 ENST00000295454.8 NP_000803.2 P18505-1X5DNL6
GABRB1XM_024453976.2 linkc.438C>T p.Ile146Ile synonymous_variant Exon 5 of 9 XP_024309744.1
GABRB1XM_024453977.2 linkc.438C>T p.Ile146Ile synonymous_variant Exon 6 of 10 XP_024309745.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GABRB1ENST00000295454.8 linkc.537C>T p.Ile179Ile synonymous_variant Exon 5 of 9 1 NM_000812.4 ENSP00000295454.3 P18505-1
GABRB1ENST00000510909.1 linkn.*205C>T non_coding_transcript_exon_variant Exon 4 of 5 4 ENSP00000426766.1 P18505-2
GABRB1ENST00000510909.1 linkn.*205C>T 3_prime_UTR_variant Exon 4 of 5 4 ENSP00000426766.1 P18505-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251052
AF XY:
0.00000737
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000140
AC:
2
AN:
1433290
Hom.:
0
Cov.:
28
AF XY:
0.00000280
AC XY:
2
AN XY:
714936
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33008
American (AMR)
AF:
0.00
AC:
0
AN:
44660
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25990
East Asian (EAS)
AF:
0.0000253
AC:
1
AN:
39576
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85740
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5734
European-Non Finnish (NFE)
AF:
9.21e-7
AC:
1
AN:
1085646
Other (OTH)
AF:
0.00
AC:
0
AN:
59530
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
CADD
Benign
11
DANN
Benign
0.83
PhyloP100
0.082

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs6284; hg19: chr4-47322219; API