chr15-27490807-T-G

Position:

• chr15-27490807-T-G

Variant summary

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

The NM_033223.5(GABRG3):​c.712+10020T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,948 control chromosomes in the GnomAD database, including 43,437 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 (43437 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.478

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRG3	NM_033223.5	c.712+10020T>G		intron_variant		ENST00000615808.5	NP_150092.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5	c.712+10020T>G		intron_variant		1	NM_033223.5	ENSP00000479113	P1
	ENST00000556642.1	n.86-7511A>C		intron_variant, non_coding_transcript_variant		2
GABRG3	ENST00000333743.10	c.175+10020T>G		intron_variant		5		ENSP00000331912
GABRG3	ENST00000554696.5	c.538+10020T>G		intron_variant		3		ENSP00000451862

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111952 AN: 151830 Hom.: 43430 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.850

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.737 AC: 112001 AN: 151948 Hom.: 43437 Cov.: 32 AF XY: 0.741 AC XY: 55059 AN XY: 74282

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.815

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.759

Gnomad4 FIN AF: 0.886

Gnomad4 NFE AF: 0.850

Gnomad4 OTH AF: 0.760

Alfa AF: 0.806 Hom.: 12274

Bravo AF: 0.721

Asia WGS AF: 0.759 AC: 2639 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	3.3
DANN	Benign	0.67

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: rs4555109; hg19: chr15-27735953;