15-27005525-C-T

Variant names:

• chr15-27005525-C-T
• rs28431127
• NM_033223.5:c.203-21229C>T

Variant summary

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

The NM_033223.5(GABRG3):​c.203-21229C>T 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 152,070 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: 0.0250
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.203-21229C>T		intron_variant	Intron 2 of 9	ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2	c.203-21229C>T		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.203-21229C>T		intron_variant	Intron 2 of 9	1	NM_033223.5	ENSP00000479113.1
GABRG3	ENST00000555083.5	c.203-21229C>T		intron_variant	Intron 2 of 5	2		ENSP00000452244.1
GABRG3	ENST00000553440.1	n.295-21229C>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73785 AN: 151952 Hom.: 18625 Cov.: 33

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.500

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: 73842 AN: 152070 Hom.: 18641 Cov.: 33 AF XY: 0.478 AC XY: 35524 AN XY: 74344

African (AFR) AF: 0.562 AC: 23322 AN: 41468

American (AMR) AF: 0.389 AC: 5947 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1767 AN: 3468

East Asian (EAS) AF: 0.104 AC: 538 AN: 5180

South Asian (SAS) AF: 0.511 AC: 2464 AN: 4820

European-Finnish (FIN) AF: 0.396 AC: 4183 AN: 10570

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 33961 AN: 67976

Other (OTH) AF: 0.499 AC: 1055 AN: 2114

Alfa AF: 0.441 Hom.: 2597

Bravo AF: 0.483

Asia WGS AF: 0.329 AC: 1148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.76
PhyloP100		0.025
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: rs28431127; hg19: chr15-27250672;