rs12372959

Variant names:

• chr15-27092509-C-T
• rs12372959
• NM_033223.5:c.270+65688C>T

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+65688C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,120 control chromosomes in the GnomAD database, including 4,240 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 0.23 (4240 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90
• Publications: 0 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)

LOC107984766 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.270+65688C>T		intron_variant	Intron 3 of 9	ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2	c.270+65688C>T		intron_variant	Intron 3 of 5		NP_001257802.1
LOC107984766	XR_001751460.2	n.225-3829G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.270+65688C>T		intron_variant	Intron 3 of 9	1	NM_033223.5	ENSP00000479113.1
GABRG3	ENST00000555083.5	c.270+65688C>T		intron_variant	Intron 3 of 5	2		ENSP00000452244.1
GABRG3-AS1	ENST00000660679.1	n.376+8314G>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34957 AN: 152002 Hom.: 4245 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0900

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.230 AC: 34955 AN: 152120 Hom.: 4240 Cov.: 32 AF XY: 0.227 AC XY: 16873 AN XY: 74344

African (AFR) AF: 0.184 AC: 7618 AN: 41496

American (AMR) AF: 0.209 AC: 3201 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1098 AN: 3472

East Asian (EAS) AF: 0.107 AC: 551 AN: 5156

South Asian (SAS) AF: 0.0900 AC: 434 AN: 4820

European-Finnish (FIN) AF: 0.270 AC: 2854 AN: 10566

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18315 AN: 67990

Other (OTH) AF: 0.246 AC: 519 AN: 2110

Alfa AF: 0.251 Hom.: 1298

Bravo AF: 0.229

Asia WGS AF: 0.114 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.52
PhyloP100		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs12372959; hg19: chr15-27337656;