rs1011456

Variant names:

• chr15-27048587-G-A
• rs1011456
• NM_033223.5:c.270+21766G>A

Variant summary

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

The NM_033223.5(GABRG3):​c.270+21766G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,014 control chromosomes in the GnomAD database, including 10,786 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 0.37 (10786 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 4 publications found

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)

LOC124903449 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.270+21766G>A		intron_variant	Intron 3 of 9	ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2	c.270+21766G>A		intron_variant	Intron 3 of 5		NP_001257802.1
LOC124903449	XR_007064545.1	n.221-7913C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.270+21766G>A		intron_variant	Intron 3 of 9	1	NM_033223.5	ENSP00000479113.1
GABRG3	ENST00000555083.5	c.270+21766G>A		intron_variant	Intron 3 of 5	2		ENSP00000452244.1
GABRG3-AS1	ENST00000660679.1	n.377-7913C>T		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56429 AN: 151896 Hom.: 10778 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.371 AC: 56462 AN: 152014 Hom.: 10786 Cov.: 32 AF XY: 0.369 AC XY: 27398 AN XY: 74310

African (AFR) AF: 0.308 AC: 12792 AN: 41492

American (AMR) AF: 0.336 AC: 5143 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1954 AN: 3472

East Asian (EAS) AF: 0.307 AC: 1576 AN: 5132

South Asian (SAS) AF: 0.404 AC: 1947 AN: 4816

European-Finnish (FIN) AF: 0.349 AC: 3688 AN: 10572

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28130 AN: 67924

Other (OTH) AF: 0.392 AC: 828 AN: 2114

Alfa AF: 0.410 Hom.: 11021

Bravo AF: 0.367

Asia WGS AF: 0.359 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.54
PhyloP100		-0.0030
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1011456; hg19: chr15-27293734;