15-27522987-C-T

Variant names:

• chr15-27522987-C-T
• rs3101644
• NM_033223.5:c.865+2863C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033223.5(GABRG3):​c.865+2863C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 151,630 control chromosomes in the GnomAD database, including 30,859 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 0.63 (30859 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705
• Publications: 5 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]

ENSG00000259168 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 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.865+2863C>T		intron	N/A	NP_150092.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG3	ENST00000615808.5	TSL:1 MANE Select	c.865+2863C>T		intron	N/A	ENSP00000479113.1
	GABRG3	ENST00000333743.10	TSL:5	c.328+2863C>T		intron	N/A	ENSP00000331912.7
	GABRG3	ENST00000554696.5	TSL:3	c.691+2863C>T		intron	N/A	ENSP00000451862.1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 94773 AN: 151512 Hom.: 30814 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.626 AC: 94876 AN: 151630 Hom.: 30859 Cov.: 32 AF XY: 0.623 AC XY: 46165 AN XY: 74112

African (AFR) AF: 0.811 AC: 33640 AN: 41462

American (AMR) AF: 0.666 AC: 10160 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1921 AN: 3462

East Asian (EAS) AF: 0.668 AC: 3450 AN: 5162

South Asian (SAS) AF: 0.546 AC: 2625 AN: 4812

European-Finnish (FIN) AF: 0.515 AC: 5435 AN: 10558

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 35823 AN: 67620

Other (OTH) AF: 0.623 AC: 1313 AN: 2106

Alfa AF: 0.554 Hom.: 35362

Bravo AF: 0.648

Asia WGS AF: 0.577 AC: 2002 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.64
PhyloP100		-0.70
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: rs3101644; hg19: chr15-27768133;