15-27490807-T-G

Variant names:

• chr15-27490807-T-G
• rs4555109
• NM_033223.5:c.712+10020T>G

Variant summary

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

The NM_033223.5(GABRG3):​c.712+10020T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,948 control chromosomes in the GnomAD database, including 43,437 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 0.74 (43437 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.478
• Publications: 1 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]

ENSG00000259168 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.712+10020T>G		intron_variant	Intron 6 of 9	ENST00000615808.5	NP_150092.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.712+10020T>G		intron_variant	Intron 6 of 9	1	NM_033223.5	ENSP00000479113.1
GABRG3	ENST00000333743.10	c.175+10020T>G		intron_variant	Intron 3 of 6	5		ENSP00000331912.7
GABRG3	ENST00000554696.5	c.538+10020T>G		intron_variant	Intron 4 of 5	3		ENSP00000451862.1
ENSG00000259168	ENST00000556642.1	n.86-7511A>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111952 AN: 151830 Hom.: 43430 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.850

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.737 AC: 112001 AN: 151948 Hom.: 43437 Cov.: 32 AF XY: 0.741 AC XY: 55059 AN XY: 74282

African (AFR) AF: 0.467 AC: 19318 AN: 41364

American (AMR) AF: 0.815 AC: 12459 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2758 AN: 3470

East Asian (EAS) AF: 0.773 AC: 3970 AN: 5136

South Asian (SAS) AF: 0.759 AC: 3656 AN: 4816

European-Finnish (FIN) AF: 0.886 AC: 9373 AN: 10578

Middle Eastern (MID) AF: 0.774 AC: 226 AN: 292

European-Non Finnish (NFE) AF: 0.850 AC: 57818 AN: 67992

Other (OTH) AF: 0.760 AC: 1605 AN: 2112

Alfa AF: 0.807 Hom.: 79876

Bravo AF: 0.721

Asia WGS AF: 0.759 AC: 2639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.67
PhyloP100		0.48
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: rs4555109; hg19: chr15-27735953;