15-26774621-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The ENST00000541819.6(GABRB3):​c.249-1849T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,194 control chromosomes in the GnomAD database, including 2,626 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 2626 hom., cov: 33)

Consequence

GABRB3
ENST00000541819.6 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.298

Publications

31 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: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.27).
BP6
Variant 15-26774621-A-G is Benign according to our data. Variant chr15-26774621-A-G is described in ClinVar as Benign. ClinVar VariationId is 3762491.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GABRB3ENST00000541819.6 linkc.249-1849T>C intron_variant Intron 2 of 9 1 ENSP00000442408.2 F5H7N0
GABRB3ENST00000557641.5 linkn.453-1849T>C intron_variant Intron 1 of 3 5

Frequencies

GnomAD3 genomes
AF:
0.159
AC:
24108
AN:
152076
Hom.:
2616
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0395
Gnomad AMI
AF:
0.167
Gnomad AMR
AF:
0.320
Gnomad ASJ
AF:
0.131
Gnomad EAS
AF:
0.316
Gnomad SAS
AF:
0.239
Gnomad FIN
AF:
0.203
Gnomad MID
AF:
0.171
Gnomad NFE
AF:
0.171
Gnomad OTH
AF:
0.167
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.158
AC:
24122
AN:
152194
Hom.:
2626
Cov.:
33
AF XY:
0.166
AC XY:
12358
AN XY:
74392
show subpopulations
African (AFR)
AF:
0.0393
AC:
1634
AN:
41540
American (AMR)
AF:
0.321
AC:
4904
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.131
AC:
454
AN:
3470
East Asian (EAS)
AF:
0.315
AC:
1629
AN:
5168
South Asian (SAS)
AF:
0.240
AC:
1157
AN:
4818
European-Finnish (FIN)
AF:
0.203
AC:
2146
AN:
10592
Middle Eastern (MID)
AF:
0.163
AC:
48
AN:
294
European-Non Finnish (NFE)
AF:
0.171
AC:
11646
AN:
67998
Other (OTH)
AF:
0.166
AC:
352
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
960
1920
2880
3840
4800
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
256
512
768
1024
1280
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.116
Hom.:
401
Bravo
AF:
0.162
Asia WGS
AF:
0.267
AC:
927
AN:
3474

ClinVar

Significance: 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 20, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.27
CADD
Benign
16
DANN
Benign
0.66
PhyloP100
0.30
Mutation Taster
=99/1
polymorphism (auto)

Splicing

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

Publications

Other links and lift over

dbSNP: rs4906902; hg19: chr15-27019768; API