rs8028997

Positions:

• chr15-26807316-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB3	ENST00000541819.6	c.248+9051C>A		intron_variant		1
GABRB3	ENST00000637226.1	n.12+9051C>A		intron_variant, non_coding_transcript_variant		5
GABRB3	ENST00000637893.1	n.41-8870C>A		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.406

Alfa AF: 0.456 Hom.: 8794

Bravo AF: 0.366

Asia WGS AF: 0.328 AC: 1142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8028997; hg19: chr15-27052463;