rs8041947

Positions:

• chr15-27071538-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.270+44717G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,184 control chromosomes in the GnomAD database, including 3,418 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 0.21 (3418 hom., cov: 33)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.270+44717G>C		intron_variant		ENST00000615808.5	NP_150092.2
LOC124903449	XR_007064545.1	n.85+483C>G		intron_variant, non_coding_transcript_variant
GABRG3	NM_001270873.2	c.270+44717G>C		intron_variant			NP_001257802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.270+44717G>C		intron_variant		1	NM_033223.5	ENSP00000479113	P1
GABRG3-AS1	ENST00000660679.1	n.376+29285C>G		intron_variant, non_coding_transcript_variant
GABRG3	ENST00000555083.5	c.270+44717G>C		intron_variant		2		ENSP00000452244

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31404 AN: 152066 Hom.: 3406 Cov.: 33

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0766

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.207 AC: 31448 AN: 152184 Hom.: 3418 Cov.: 33 AF XY: 0.201 AC XY: 14948 AN XY: 74394

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.0769

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.207

Alfa AF: 0.217 Hom.: 440

Bravo AF: 0.211

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.61
DANN	Benign	0.47

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: rs8041947; hg19: chr15-27316685;