chr15-27208761-A-G

Variant names:

• chr15-27208761-A-G
• rs968671
• NM_033223.5:c.271-118048A>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.271-118048A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0342 in 152,408 control chromosomes in the GnomAD database, including 168 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 0.034 (168 hom., cov: 33)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324
• 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]

ENSG00000214254 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0794 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.271-118048A>G		intron	N/A	NP_150092.2
	GABRG3	NM_001270873.2		c.271-118048A>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.271-118048A>G		intron	N/A	ENSP00000479113.1
	GABRG3	ENST00000555083.5	TSL:2	c.271-118048A>G		intron	N/A	ENSP00000452244.1
	ENSG00000214254	ENST00000438334.1	TSL:6	n.-126T>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0341 AC: 5184 AN: 152116 Hom.: 168 Cov.: 33

Gnomad AFR AF: 0.0816

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.00540

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0349

GnomAD4 exome AF: 0.0115 AC: 2 AN: 174 Hom.: 0 AF XY: 0.0111 AC XY: 1 AN XY: 90

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 10

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0154 AC: 2 AN: 130

Other (OTH) AF: 0.00 AC: 0 AN: 20

GnomAD4 genome AF: 0.0342 AC: 5203 AN: 152234 Hom.: 168 Cov.: 33 AF XY: 0.0329 AC XY: 2448 AN XY: 74424

African (AFR) AF: 0.0817 AC: 3395 AN: 41540

American (AMR) AF: 0.0157 AC: 240 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3470

East Asian (EAS) AF: 0.00541 AC: 28 AN: 5176

South Asian (SAS) AF: 0.0185 AC: 89 AN: 4816

European-Finnish (FIN) AF: 0.0127 AC: 135 AN: 10604

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0169 AC: 1151 AN: 68008

Other (OTH) AF: 0.0346 AC: 73 AN: 2112

Alfa AF: 0.0267 Hom.: 161

Bravo AF: 0.0351

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.84
DANN	Benign	0.48
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: rs968671; hg19: chr15-27453908;