15-27079795-A-G

Variant names:

• chr15-27079795-A-G
• rs4887549
• NM_033223.5:c.270+52974A>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.270+52974A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,154 control chromosomes in the GnomAD database, including 3,320 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 0.20 (3320 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321
• 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]

GABRG3-AS1 (HGNC:40249): (GABRG3 antisense RNA 1)

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 (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033223.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG3	NM_033223.5	MANE Select	c.270+52974A>G		intron	N/A	NP_150092.2
	GABRG3	NM_001270873.2		c.270+52974A>G		intron	N/A	NP_001257802.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG3	ENST00000615808.5	TSL:1 MANE Select	c.270+52974A>G		intron	N/A	ENSP00000479113.1
	GABRG3	ENST00000555083.5	TSL:2	c.270+52974A>G		intron	N/A	ENSP00000452244.1
	GABRG3-AS1	ENST00000660679.1		n.376+21028T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31058 AN: 152036 Hom.: 3315 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0771

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.204 AC: 31088 AN: 152154 Hom.: 3320 Cov.: 32 AF XY: 0.199 AC XY: 14778 AN XY: 74364

African (AFR) AF: 0.251 AC: 10430 AN: 41486

American (AMR) AF: 0.155 AC: 2366 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 762 AN: 3472

East Asian (EAS) AF: 0.116 AC: 602 AN: 5180

South Asian (SAS) AF: 0.0774 AC: 374 AN: 4832

European-Finnish (FIN) AF: 0.154 AC: 1632 AN: 10584

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14195 AN: 67988

Other (OTH) AF: 0.204 AC: 430 AN: 2108

Alfa AF: 0.203 Hom.: 557

Bravo AF: 0.208

Asia WGS AF: 0.120 AC: 419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.49
PhyloP100		-0.32
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: rs4887549; hg19: chr15-27324942;