NM_033223.5:c.270+51231T>C

Variant names:

• chr15-27078052-T-C
• rs7179575
• NM_033223.5:c.270+51231T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033223.5(GABRG3):​c.270+51231T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,138 control chromosomes in the GnomAD database, including 43,334 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 0.74 (43334 hom., cov: 33)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 4 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033223.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG3	NM_033223.5	MANE Select	c.270+51231T>C		intron	N/A	NP_150092.2
	GABRG3	NM_001270873.2		c.270+51231T>C		intron	N/A	NP_001257802.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG3	ENST00000615808.5	TSL:1 MANE Select	c.270+51231T>C		intron	N/A	ENSP00000479113.1
	GABRG3	ENST00000555083.5	TSL:2	c.270+51231T>C		intron	N/A	ENSP00000452244.1
	GABRG3-AS1	ENST00000660679.1		n.376+22771A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112794 AN: 152020 Hom.: 43271 Cov.: 33

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.742 AC: 112917 AN: 152138 Hom.: 43334 Cov.: 33 AF XY: 0.743 AC XY: 55282 AN XY: 74380

African (AFR) AF: 0.936 AC: 38880 AN: 41538

American (AMR) AF: 0.698 AC: 10665 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2137 AN: 3468

East Asian (EAS) AF: 0.907 AC: 4690 AN: 5172

South Asian (SAS) AF: 0.702 AC: 3383 AN: 4820

European-Finnish (FIN) AF: 0.682 AC: 7212 AN: 10572

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.644 AC: 43749 AN: 67970

Other (OTH) AF: 0.694 AC: 1462 AN: 2106

Alfa AF: 0.670 Hom.: 36668

Bravo AF: 0.754

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.055
DANN	Benign	0.33
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7179575; hg19: chr15-27323199; COSMIC: COSV61520751;