15-27094565-G-A

Variant names:

• chr15-27094565-G-A
• rs4555125
• NM_033223.5:c.270+67744G>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.270+67744G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,064 control chromosomes in the GnomAD database, including 5,317 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 0.26 (5317 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646
• 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)

LOC107984766 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG3	NM_033223.5	MANE Select	c.270+67744G>A		intron	N/A	NP_150092.2
	GABRG3	NM_001270873.2		c.270+67744G>A		intron	N/A	NP_001257802.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG3	ENST00000615808.5	TSL:1 MANE Select	c.270+67744G>A		intron	N/A	ENSP00000479113.1
	GABRG3	ENST00000555083.5	TSL:2	c.270+67744G>A		intron	N/A	ENSP00000452244.1
	GABRG3-AS1	ENST00000660679.1		n.376+6258C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39532 AN: 151944 Hom.: 5311 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.340

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.260 AC: 39569 AN: 152064 Hom.: 5317 Cov.: 32 AF XY: 0.257 AC XY: 19093 AN XY: 74332

African (AFR) AF: 0.287 AC: 11911 AN: 41470

American (AMR) AF: 0.221 AC: 3382 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1103 AN: 3472

East Asian (EAS) AF: 0.114 AC: 588 AN: 5162

South Asian (SAS) AF: 0.0848 AC: 408 AN: 4814

European-Finnish (FIN) AF: 0.270 AC: 2864 AN: 10590

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.270 AC: 18376 AN: 67954

Other (OTH) AF: 0.268 AC: 568 AN: 2116

Alfa AF: 0.222 Hom.: 1347

Bravo AF: 0.262

Asia WGS AF: 0.124 AC: 433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.17
DANN	Benign	0.34
PhyloP100		-0.65
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: rs4555125; hg19: chr15-27339712;