rs1367959

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000814.6(GABRB3):​c.241-50477G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 151,948 control chromosomes in the GnomAD database, including 5,291 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 5291 hom., cov: 32)

Consequence

GABRB3
NM_000814.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.138
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GABRB3NM_000814.6 linkuse as main transcriptc.241-50477G>A intron_variant ENST00000311550.10
GABRB3NM_001191320.2 linkuse as main transcriptc.-16+44603G>A intron_variant
GABRB3NM_001278631.2 linkuse as main transcriptc.-111-29483G>A intron_variant
GABRB3NM_021912.5 linkuse as main transcriptc.241-50477G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GABRB3ENST00000311550.10 linkuse as main transcriptc.241-50477G>A intron_variant 1 NM_000814.6 P1P28472-1

Frequencies

GnomAD3 genomes
AF:
0.238
AC:
36160
AN:
151830
Hom.:
5286
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0614
Gnomad AMI
AF:
0.343
Gnomad AMR
AF:
0.328
Gnomad ASJ
AF:
0.199
Gnomad EAS
AF:
0.320
Gnomad SAS
AF:
0.322
Gnomad FIN
AF:
0.327
Gnomad MID
AF:
0.161
Gnomad NFE
AF:
0.300
Gnomad OTH
AF:
0.240
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.238
AC:
36171
AN:
151948
Hom.:
5291
Cov.:
32
AF XY:
0.241
AC XY:
17904
AN XY:
74256
show subpopulations
Gnomad4 AFR
AF:
0.0612
Gnomad4 AMR
AF:
0.329
Gnomad4 ASJ
AF:
0.199
Gnomad4 EAS
AF:
0.320
Gnomad4 SAS
AF:
0.323
Gnomad4 FIN
AF:
0.327
Gnomad4 NFE
AF:
0.300
Gnomad4 OTH
AF:
0.239
Alfa
AF:
0.287
Hom.:
3418
Bravo
AF:
0.231
Asia WGS
AF:
0.324
AC:
1128
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
4.4
DANN
Benign
0.38

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.

Other links and lift over

dbSNP: rs1367959; hg19: chr15-26917158; API