chr15-27048216-A-G

Variant names:

• chr15-27048216-A-G
• rs1011455
• NM_033223.5:c.270+21395A>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.270+21395A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 151,912 control chromosomes in the GnomAD database, including 19,900 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 0.50 (19900 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.58
• 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]

GABRG3-AS1 (HGNC:40249): (GABRG3 antisense RNA 1)

LOC124903449 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.270+21395A>G		intron_variant	Intron 3 of 9	ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2	c.270+21395A>G		intron_variant	Intron 3 of 5		NP_001257802.1
LOC124903449	XR_007064545.1	n.221-7542T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.270+21395A>G		intron_variant	Intron 3 of 9	1	NM_033223.5	ENSP00000479113.1
GABRG3	ENST00000555083.5	c.270+21395A>G		intron_variant	Intron 3 of 5	2		ENSP00000452244.1
GABRG3-AS1	ENST00000660679.1	n.377-7542T>C		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76546 AN: 151796 Hom.: 19856 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.505 AC: 76642 AN: 151912 Hom.: 19900 Cov.: 32 AF XY: 0.506 AC XY: 37539 AN XY: 74216

African (AFR) AF: 0.608 AC: 25200 AN: 41432

American (AMR) AF: 0.587 AC: 8961 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1902 AN: 3464

East Asian (EAS) AF: 0.612 AC: 3147 AN: 5138

South Asian (SAS) AF: 0.515 AC: 2476 AN: 4806

European-Finnish (FIN) AF: 0.383 AC: 4047 AN: 10566

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29396 AN: 67922

Other (OTH) AF: 0.498 AC: 1051 AN: 2112

Alfa AF: 0.452 Hom.: 31080

Bravo AF: 0.525

Asia WGS AF: 0.560 AC: 1949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.031
DANN	Benign	0.40
PhyloP100		-4.6
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: rs1011455; hg19: chr15-27293363;