rs6576629

Variant names:

• chr15-26820960-C-A
• rs6576629
• ENST00000541819.6:c.201-4546G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-26820960-C-A
• chr15-26820960-C-G
• chr15-26820960-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000541819.6(GABRB3):​c.201-4546G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 152,132 control chromosomes in the GnomAD database, including 58,288 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 0.87 (58288 hom., cov: 31)
• Consequence: GABRB3 ENST00000541819.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.622
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.948 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
GABRB3	ENST00000541819.6	c.201-4546G>T		intron_variant	Intron 1 of 9	1		ENSP00000442408.2

Frequencies

GnomAD3 genomes AF: 0.868 AC: 131939 AN: 152014 Hom.: 58261 Cov.: 31

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.948

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.874

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.884

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.868 AC: 132013 AN: 152132 Hom.: 58288 Cov.: 31 AF XY: 0.870 AC XY: 64747 AN XY: 74392

African (AFR) AF: 0.690 AC: 28616 AN: 41444

American (AMR) AF: 0.917 AC: 14026 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.874 AC: 3033 AN: 3470

East Asian (EAS) AF: 0.796 AC: 4119 AN: 5174

South Asian (SAS) AF: 0.835 AC: 4017 AN: 4810

European-Finnish (FIN) AF: 0.973 AC: 10326 AN: 10616

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.954 AC: 64875 AN: 68006

Other (OTH) AF: 0.886 AC: 1872 AN: 2114

Alfa AF: 0.908 Hom.: 3211

Bravo AF: 0.856

Asia WGS AF: 0.789 AC: 2746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.28
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6576629; hg19: chr15-27066107;