rs2114485

chr15-26557677-G-Achr15-26557677-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000814.6(GABRB3):c.1080+3255C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 151,942 control chromosomes in the GnomAD database, including 33,349 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 0.65 (33349 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GABRB3 NM_000814.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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]

(HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB3	NM_000814.6	c.1080+3255C>T		intron_variant		ENST00000311550.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB3	ENST00000311550.10	c.1080+3255C>T		intron_variant		1	NM_000814.6	P1
	ENST00000621819.1	n.261C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99049 AN: 151824 Hom.: 33341 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.681

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.652 AC: 99102 AN: 151942 Hom.: 33349 Cov.: 32 AF XY: 0.650 AC XY: 48244 AN XY: 74254

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.682

Alfa AF: 0.666 Hom.: 6196

Bravo AF: 0.642

Asia WGS AF: 0.470 AC: 1629 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.62
Dann	Benign	0.49

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

Other links and lift over

dbSNP: rs2114485; hg19: chr15-26802824;