rs4555125

chr15-27094565-G-Achr15-27094565-G-T

Variant summary

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

The NM_033223.5(GABRG3):c.270+67744G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,064 control chromosomes in the GnomAD database, including 5,317 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 (5317 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG3	NM_033223.5	c.270+67744G>A		intron_variant		ENST00000615808.5
LOC107984766	XR_001751460.2	n.224+4251C>T		intron_variant, non_coding_transcript_variant
GABRG3	NM_001270873.2	c.270+67744G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG3	ENST00000615808.5	c.270+67744G>A		intron_variant		1	NM_033223.5	P1
GABRG3-AS1	ENST00000660679.1	n.376+6258C>T		intron_variant, non_coding_transcript_variant
GABRG3	ENST00000555083.5	c.270+67744G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39532 AN: 151944 Hom.: 5311 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.340

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.260 AC: 39569 AN: 152064 Hom.: 5317 Cov.: 32 AF XY: 0.257 AC XY: 19093 AN XY: 74332

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.0848

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.268

Alfa AF: 0.190 Hom.: 495

Bravo AF: 0.262

Asia WGS AF: 0.124 AC: 433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.17
Dann	Benign	0.34

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: rs4555125; hg19: chr15-27339712;