rs7180500

Variant names:

• chr15-27008032-C-A
• rs7180500
• NM_033223.5:c.203-18722C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-27008032-C-A
• chr15-27008032-C-G

Variant summary

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

The NM_033223.5(GABRG3):​c.203-18722C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,992 control chromosomes in the GnomAD database, including 18,641 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 0.49 (18641 hom., cov: 33)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.490

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.203-18722C>A		intron_variant	Intron 2 of 9	ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2	c.203-18722C>A		intron_variant	Intron 2 of 5		NP_001257802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.203-18722C>A		intron_variant	Intron 2 of 9	1	NM_033223.5	ENSP00000479113.1
GABRG3	ENST00000555083.5	c.203-18722C>A		intron_variant	Intron 2 of 5	2		ENSP00000452244.1
GABRG3	ENST00000553440.1	n.295-18722C>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73775 AN: 151874 Hom.: 18625 Cov.: 33

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.486 AC: 73833 AN: 151992 Hom.: 18641 Cov.: 33 AF XY: 0.478 AC XY: 35495 AN XY: 74302

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.499

Alfa AF: 0.342 Hom.: 840

Bravo AF: 0.484

Asia WGS AF: 0.325 AC: 1133 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.066
DANN	Benign	0.32

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: rs7180500; hg19: chr15-27253179; COSMIC: COSV61536637;