rs8028997

Variant names:

• chr15-26807316-G-T
• rs8028997
• ENST00000541819.6:c.248+9051C>A

Variant summary

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

The ENST00000541819.6(GABRB3):​c.248+9051C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,022 control chromosomes in the GnomAD database, including 12,398 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 0.39 (12398 hom., cov: 32)
• Consequence: GABRB3 ENST00000541819.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000541819.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB3	ENST00000541819.6	TSL:1	c.248+9051C>A		intron	N/A	ENSP00000442408.2
	GABRB3	ENST00000637226.1	TSL:5	n.12+9051C>A		intron	N/A
	GABRB3	ENST00000637893.1	TSL:5	n.41-8870C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58712 AN: 151904 Hom.: 12391 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.386 AC: 58728 AN: 152022 Hom.: 12398 Cov.: 32 AF XY: 0.386 AC XY: 28652 AN XY: 74298

African (AFR) AF: 0.235 AC: 9739 AN: 41486

American (AMR) AF: 0.339 AC: 5172 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1442 AN: 3464

East Asian (EAS) AF: 0.189 AC: 977 AN: 5174

South Asian (SAS) AF: 0.481 AC: 2315 AN: 4814

European-Finnish (FIN) AF: 0.514 AC: 5428 AN: 10562

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32161 AN: 67942

Other (OTH) AF: 0.406 AC: 854 AN: 2102

Alfa AF: 0.453 Hom.: 11757

Bravo AF: 0.366

Asia WGS AF: 0.328 AC: 1142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.81
PhyloP100		-0.42
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: rs8028997; hg19: chr15-27052463;