rs4398085

Variant names:

• chr15-27096807-C-T
• rs4398085
• NM_033223.5:c.270+69986C>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.270+69986C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 150,348 control chromosomes in the GnomAD database, including 5,300 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 (5300 hom., cov: 30)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.270+69986C>T		intron_variant	Intron 3 of 9	ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2	c.270+69986C>T		intron_variant	Intron 3 of 5		NP_001257802.1
LOC107984766	XR_001751460.2	n.224+2009G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.270+69986C>T		intron_variant	Intron 3 of 9	1	NM_033223.5	ENSP00000479113.1
GABRG3	ENST00000555083.5	c.270+69986C>T		intron_variant	Intron 3 of 5	2		ENSP00000452244.1
GABRG3-AS1	ENST00000660679.1	n.376+4016G>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39216 AN: 150260 Hom.: 5298 Cov.: 30

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0856

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.343

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.261 AC: 39240 AN: 150348 Hom.: 5300 Cov.: 30 AF XY: 0.257 AC XY: 18875 AN XY: 73338

African (AFR) AF: 0.278 AC: 11381 AN: 40930

American (AMR) AF: 0.224 AC: 3401 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1108 AN: 3464

East Asian (EAS) AF: 0.108 AC: 547 AN: 5068

South Asian (SAS) AF: 0.0859 AC: 407 AN: 4736

European-Finnish (FIN) AF: 0.275 AC: 2753 AN: 9994

Middle Eastern (MID) AF: 0.334 AC: 97 AN: 290

European-Non Finnish (NFE) AF: 0.276 AC: 18713 AN: 67710

Other (OTH) AF: 0.269 AC: 562 AN: 2090

Alfa AF: 0.260 Hom.: 2986

Bravo AF: 0.262

Asia WGS AF: 0.118 AC: 414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.44
PhyloP100		-0.50
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: rs4398085; hg19: chr15-27341954;