rs3097490

Positions:

• chr15-27528645-G-A
• chr15-27528645-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033223.5(GABRG3):​c.1122+653G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,946 control chromosomes in the GnomAD database, including 26,976 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 0.59 (26976 hom., cov: 33)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG3	NM_033223.5	c.1122+653G>A		intron_variant		ENST00000615808.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG3	ENST00000615808.5	c.1122+653G>A		intron_variant		1	NM_033223.5	P1
	ENST00000556642.1	n.85+12468C>T		intron_variant, non_coding_transcript_variant		2
GABRG3	ENST00000333743.10	c.585+653G>A		intron_variant		5
GABRG3	ENST00000451330.2	c.410+653G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89718 AN: 151828 Hom.: 26942 Cov.: 33

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.591 AC: 89801 AN: 151946 Hom.: 26976 Cov.: 33 AF XY: 0.589 AC XY: 43767 AN XY: 74252

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.601

Alfa AF: 0.580 Hom.: 4386

Bravo AF: 0.610

Asia WGS AF: 0.588 AC: 2045 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	0.96
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs3097490; hg19: chr15-27773791;