chr15-26773704-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The ENST00000299267.9(GABRB3):​c.21G>A​(p.Glu7Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,420,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

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

Consequence

GABRB3
ENST00000299267.9 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.82

Publications

0 publications found
Variant links:
Genes affected
GABRB3 (HGNC:4083): (gamma-aminobutyric acid type A receptor subunit beta3) This gene encodes a member of the ligand-gated ionic channel family. The encoded protein is one the subunits of a multi-subunit chloride channel that serves as the receptor for gamma-aminobutyric acid, a major inhibitory neurotransmitter of the mammalian nervous system. This gene is located on the long arm of chromosome 15 in a cluster with two other genes encoding related subunits of the family. This gene may be associated with the pathogenesis of several disorders including Angelman syndrome, Prader-Willi syndrome, nonsyndromic orofacial clefts, epilepsy and autism. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2013]
GABRB3 Gene-Disease associations (from GenCC):
  • developmental and epileptic encephalopathy, 43
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • epilepsy, childhood absence, susceptibility to, 5
    Inheritance: AD, Unknown Classification: DEFINITIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
  • genetic developmental and epileptic encephalopathy
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • childhood absence epilepsy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Lennox-Gastaut syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant 15-26773704-C-T is Benign according to our data. Variant chr15-26773704-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 415891.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.83 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GABRB3NM_021912.5 linkc.21G>A p.Glu7Glu synonymous_variant Exon 1 of 9 NP_068712.1 P28472-2B2RCW8X5DQY4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GABRB3ENST00000299267.9 linkc.21G>A p.Glu7Glu synonymous_variant Exon 1 of 9 1 ENSP00000299267.4 P28472-2
GABRB3ENST00000541819.6 linkc.249-932G>A intron_variant Intron 2 of 9 1 ENSP00000442408.2 F5H7N0
GABRB3ENST00000554722.1 linkn.48G>A non_coding_transcript_exon_variant Exon 1 of 4 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000141
AC:
2
AN:
1420546
Hom.:
0
Cov.:
32
AF XY:
0.00000142
AC XY:
1
AN XY:
702552
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32696
American (AMR)
AF:
0.00
AC:
0
AN:
38734
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25360
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37760
South Asian (SAS)
AF:
0.00
AC:
0
AN:
80834
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49044
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5542
European-Non Finnish (NFE)
AF:
0.00000183
AC:
2
AN:
1091748
Other (OTH)
AF:
0.00
AC:
0
AN:
58828
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.600
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

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Epilepsy, childhood absence, susceptibility to, 1;C2677087:Epilepsy, childhood absence, susceptibility to, 5 Benign:1
Jan 28, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely 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
-0.73
CADD
Benign
5.9
DANN
Benign
0.93
PhyloP100
-1.8
PromoterAI
0.010
Neutral

Splicing

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

Publications

Other links and lift over

dbSNP: rs1060504683; hg19: chr15-27018851; API