chr15-27224754-A-G

Variant names:

• chr15-27224754-A-G
• rs897173
• NM_033223.5:c.271-102055A>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.271-102055A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,194 control chromosomes in the GnomAD database, including 10,758 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 0.33 (10758 hom., cov: 33)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 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.271-102055A>G		intron	N/A	NP_150092.2
	GABRG3	NM_001270873.2		c.271-102055A>G		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.271-102055A>G		intron	N/A	ENSP00000479113.1
	GABRG3	ENST00000555083.5	TSL:2	c.271-102055A>G		intron	N/A	ENSP00000452244.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49802 AN: 152076 Hom.: 10729 Cov.: 33

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.328 AC: 49892 AN: 152194 Hom.: 10758 Cov.: 33 AF XY: 0.329 AC XY: 24447 AN XY: 74416

African (AFR) AF: 0.597 AC: 24797 AN: 41530

American (AMR) AF: 0.285 AC: 4364 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 810 AN: 3470

East Asian (EAS) AF: 0.480 AC: 2477 AN: 5162

South Asian (SAS) AF: 0.427 AC: 2058 AN: 4822

European-Finnish (FIN) AF: 0.140 AC: 1489 AN: 10608

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12998 AN: 67996

Other (OTH) AF: 0.315 AC: 665 AN: 2114

Alfa AF: 0.251 Hom.: 17307

Bravo AF: 0.349

Asia WGS AF: 0.489 AC: 1697 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	0.067
DANN	Benign	0.39
PhyloP100		-2.2
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: rs897173; hg19: chr15-27469901;