rs891802

Variant names:

• chr15-27031472-C-T
• rs891802
• NM_033223.5:c.270+4651C>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+4651C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,002 control chromosomes in the GnomAD database, including 31,870 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 0.65 (31870 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 2 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.270+4651C>T		intron_variant	Intron 3 of 9	ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2	c.270+4651C>T		intron_variant	Intron 3 of 5		NP_001257802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.270+4651C>T		intron_variant	Intron 3 of 9	1	NM_033223.5	ENSP00000479113.1
GABRG3	ENST00000555083.5	c.270+4651C>T		intron_variant	Intron 3 of 5	2		ENSP00000452244.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98227 AN: 151884 Hom.: 31844 Cov.: 32

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.647 AC: 98314 AN: 152002 Hom.: 31870 Cov.: 32 AF XY: 0.649 AC XY: 48217 AN XY: 74306

African (AFR) AF: 0.670 AC: 27754 AN: 41424

American (AMR) AF: 0.649 AC: 9914 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2386 AN: 3472

East Asian (EAS) AF: 0.680 AC: 3518 AN: 5172

South Asian (SAS) AF: 0.658 AC: 3170 AN: 4818

European-Finnish (FIN) AF: 0.650 AC: 6864 AN: 10566

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42508 AN: 67952

Other (OTH) AF: 0.643 AC: 1358 AN: 2112

Alfa AF: 0.630 Hom.: 11317

Bravo AF: 0.648

Asia WGS AF: 0.671 AC: 2333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.61
PhyloP100		-2.0
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: rs891802; hg19: chr15-27276619;