rs4887551

Positions:

• chr15-27081215-G-A

Variant summary

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

The NM_033223.5(GABRG3):​c.270+54394G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,988 control chromosomes in the GnomAD database, including 2,921 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 0.19 (2921 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410

Genes affected

GABRG3 (HGNC:4088): (gamma-aminobutyric acid type A receptor subunit gamma3) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. The protein encoded by this gene is a gamma subunit, which contains the benzodiazepine binding site. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Aug 2012]

GABRG3-AS1 (HGNC:40249): (GABRG3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.270+54394G>A		intron_variant		ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2	c.270+54394G>A		intron_variant			NP_001257802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.270+54394G>A		intron_variant		1	NM_033223.5	ENSP00000479113	P1
GABRG3-AS1	ENST00000660679.1	n.376+19608C>T		intron_variant, non_coding_transcript_variant
GABRG3	ENST00000555083.5	c.270+54394G>A		intron_variant		2		ENSP00000452244

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29325 AN: 151872 Hom.: 2918 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0767

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.193 AC: 29346 AN: 151988 Hom.: 2921 Cov.: 32 AF XY: 0.189 AC XY: 14013 AN XY: 74310

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.0766

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.197

Alfa AF: 0.200 Hom.: 2861

Bravo AF: 0.196

Asia WGS AF: 0.116 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.25

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: rs4887551; hg19: chr15-27326362;