dbSNP rs2017247: GABRB3:c.*3778A>G (chr15-26544015-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000814.6(GABRB3):c.*3778A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,536 control chromosomes in the GnomAD database, including 46,257 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 0.77 ( 46164 hom., cov: 32)

Exomes 𝑓: 0.70 ( 93 hom. )

Consequence

GABRB3
NM_000814.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.135

Publications

11 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

GABRB3 links:

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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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB3	NM_000814.6 link	c.*3778A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000311550.10	NP_000805.1	P28472-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000311550.10 link	c.*3778A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_000814.6	ENSP00000308725.5		P28472-1

Frequencies

GnomAD3 genomes

AF:

0.769

AC:

116861

AN:

152016

Hom.:

46117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.919

Gnomad AMI

AF:

0.692

Gnomad AMR

AF:

0.748

Gnomad ASJ

AF:

0.726

Gnomad EAS

AF:

0.283

Gnomad SAS

AF:

0.616

Gnomad FIN

AF:

0.724

Gnomad MID

AF:

0.785

Gnomad NFE

AF:

0.740

Gnomad OTH

AF:

0.766

GnomAD4 exome

AF:

0.697

AC:

280

AN:

402

Hom.:

Cov.:

AF XY:

0.702

AC XY:

167

AN XY:

238

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.697

AC:

276

AN:

396

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.769

AC:

116965

AN:

152134

Hom.:

46164

Cov.:

AF XY:

0.762

AC XY:

56680

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.920

AC:

38173

AN:

41514

American (AMR)

AF:

0.747

AC:

11412

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.726

AC:

2520

AN:

3470

East Asian (EAS)

AF:

0.284

AC:

1466

AN:

5166

South Asian (SAS)

AF:

0.615

AC:

2961

AN:

4816

European-Finnish (FIN)

AF:

0.724

AC:

7652

AN:

10576

Middle Eastern (MID)

AF:

0.782

AC:

230

AN:

294

European-Non Finnish (NFE)

AF:

0.740

AC:

50303

AN:

67994

Other (OTH)

AF:

0.766

AC:

1617

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1256

2513

3769

5026

6282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.763

Hom.:

11029

Bravo

AF:

0.777

Asia WGS

AF:

0.527

AC:

1836

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.6

(source)

DANN

Benign

0.68

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs2017247

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over