chr15-27016500-A-G

Variant names:

• chr15-27016500-A-G
• rs2195817
• NM_033223.5:c.203-10254A>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.203-10254A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,912 control chromosomes in the GnomAD database, including 24,130 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 0.56 (24130 hom., cov: 31)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.369
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.203-10254A>G		intron_variant	Intron 2 of 9	ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2	c.203-10254A>G		intron_variant	Intron 2 of 5		NP_001257802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.203-10254A>G		intron_variant	Intron 2 of 9	1	NM_033223.5	ENSP00000479113.1
GABRG3	ENST00000555083.5	c.203-10254A>G		intron_variant	Intron 2 of 5	2		ENSP00000452244.1
GABRG3	ENST00000553440.1	n.295-10254A>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84661 AN: 151792 Hom.: 24095 Cov.: 31

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.558 AC: 84749 AN: 151912 Hom.: 24130 Cov.: 31 AF XY: 0.551 AC XY: 40909 AN XY: 74272

African (AFR) AF: 0.636 AC: 26324 AN: 41404

American (AMR) AF: 0.472 AC: 7212 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1870 AN: 3468

East Asian (EAS) AF: 0.282 AC: 1462 AN: 5176

South Asian (SAS) AF: 0.554 AC: 2665 AN: 4814

European-Finnish (FIN) AF: 0.478 AC: 5036 AN: 10530

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38343 AN: 67932

Other (OTH) AF: 0.571 AC: 1208 AN: 2116

Alfa AF: 0.551 Hom.: 5097

Bravo AF: 0.556

Asia WGS AF: 0.429 AC: 1495 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	6.2
DANN	Benign	0.77
PhyloP100		0.37
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: rs2195817; hg19: chr15-27261647;