NM_033223.5:c.574+33340G>A

Variant names:

• chr15-27362228-G-A
• rs9744111
• NM_033223.5:c.574+33340G>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.574+33340G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,088 control chromosomes in the GnomAD database, including 11,019 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 0.35 (11019 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632
• 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]

ENSG00000261426 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.574+33340G>A		intron_variant	Intron 5 of 9	ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2	c.574+33340G>A		intron_variant	Intron 5 of 5		NP_001257802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.574+33340G>A		intron_variant	Intron 5 of 9	1	NM_033223.5	ENSP00000479113.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52685 AN: 151970 Hom.: 10998 Cov.: 33

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.347 AC: 52760 AN: 152088 Hom.: 11019 Cov.: 33 AF XY: 0.348 AC XY: 25842 AN XY: 74352

African (AFR) AF: 0.580 AC: 24042 AN: 41456

American (AMR) AF: 0.394 AC: 6023 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1107 AN: 3472

East Asian (EAS) AF: 0.159 AC: 823 AN: 5174

South Asian (SAS) AF: 0.331 AC: 1595 AN: 4826

European-Finnish (FIN) AF: 0.229 AC: 2424 AN: 10588

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.229 AC: 15584 AN: 67984

Other (OTH) AF: 0.360 AC: 758 AN: 2106

Alfa AF: 0.295 Hom.: 995

Bravo AF: 0.368

Asia WGS AF: 0.274 AC: 952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.52
DANN	Benign	0.34
PhyloP100		-0.63
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: rs9744111; hg19: chr15-27607374;