rs1863456

Positions:

• chr15-26728885-G-A

Variant summary

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

The NM_000814.6(GABRB3):​c.240+43517C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,990 control chromosomes in the GnomAD database, including 16,210 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 0.43 (16210 hom., cov: 32)
• Consequence: GABRB3 NM_000814.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990

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 (AMR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRB3	NM_000814.6	c.240+43517C>T		intron_variant		ENST00000311550.10	NP_000805.1
GABRB3	NM_001278631.2	c.-112+43517C>T		intron_variant			NP_001265560.1
GABRB3	NM_021912.5	c.240+43517C>T		intron_variant			NP_068712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000311550.10	c.240+43517C>T		intron_variant		1	NM_000814.6	ENSP00000308725	P1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64764 AN: 151872 Hom.: 16196 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.426 AC: 64783 AN: 151990 Hom.: 16210 Cov.: 32 AF XY: 0.431 AC XY: 32052 AN XY: 74294

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.578

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.459

Alfa AF: 0.478 Hom.: 3091

Bravo AF: 0.419

Asia WGS AF: 0.595 AC: 2069 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	1.7
DANN	Benign	0.68

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: rs1863456; hg19: chr15-26974032;