rs74006954

Variant names:

• chr15-27467498-G-A
• rs74006954
• NM_033223.5:c.575-13152G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-27467498-G-A
• chr15-27467498-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.575-13152G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 152,266 control chromosomes in the GnomAD database, including 1,342 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 0.099 (1342 hom., cov: 33)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.575-13152G>A		intron_variant	Intron 5 of 9	ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2	c.575-13152G>A		intron_variant	Intron 5 of 5		NP_001257802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.575-13152G>A		intron_variant	Intron 5 of 9	1	NM_033223.5	ENSP00000479113.1
GABRG3	ENST00000333743.10	c.38-13152G>A		intron_variant	Intron 2 of 6	5		ENSP00000331912.7
GABRG3	ENST00000554696.5	c.401-13152G>A		intron_variant	Intron 3 of 5	3		ENSP00000451862.1
GABRG3	ENST00000555083.5	c.575-13152G>A		intron_variant	Intron 5 of 5	2		ENSP00000452244.1

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15064 AN: 152148 Hom.: 1342 Cov.: 33

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0433

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0508

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0347

Gnomad OTH AF: 0.0635

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

GnomAD4 genome AF: 0.0990 AC: 15080 AN: 152266 Hom.: 1342 Cov.: 33 AF XY: 0.0981 AC XY: 7300 AN XY: 74446

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.0431

Gnomad4 ASJ AF: 0.0280

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0508

Gnomad4 NFE AF: 0.0347

Gnomad4 OTH AF: 0.0619

Alfa AF: 0.0181 Hom.: 16

Bravo AF: 0.103

Asia WGS AF: 0.145 AC: 501 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	0.19
DANN	Benign	0.62

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: rs74006954; hg19: chr15-27712644;