rs6627221

Variant names:

• chrX-152247402-T-C
• rs6627221
• NM_000808.4:c.551+8376A>G

Variant summary

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

The NM_000808.4(GABRA3):​c.551+8376A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 110,134 control chromosomes in the GnomAD database, including 3,562 homozygotes. There are 8,690 hemizygotes in GnomAD. 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 0.27 (3562 hom., 8690 hem., cov: 22)
• Consequence: GABRA3 NM_000808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 2 publications found

Genes affected

GABRA3 (HGNC:4077): (gamma-aminobutyric acid type A receptor subunit alpha3) 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. At least 16 distinct subunits of GABA-A receptors have been identified. [provided by RefSeq, Jul 2008]

GABRA3 Gene-Disease associations (from GenCC):

• epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA3	NM_000808.4	c.551+8376A>G		intron_variant	Intron 5 of 9	ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4	c.551+8376A>G		intron_variant	Intron 5 of 8		XP_006724874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA3	ENST00000370314.9	c.551+8376A>G		intron_variant	Intron 5 of 9	1	NM_000808.4	ENSP00000359337.4
GABRA3	ENST00000535043.1	c.551+8376A>G		intron_variant	Intron 5 of 9	1		ENSP00000443527.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 30134 AN: 110081 Hom.: 3558 Cov.: 22

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.274 AC: 30181 AN: 110134 Hom.: 3562 Cov.: 22 AF XY: 0.267 AC XY: 8690 AN XY: 32524

African (AFR) AF: 0.425 AC: 12877 AN: 30274

American (AMR) AF: 0.339 AC: 3481 AN: 10266

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 453 AN: 2637

East Asian (EAS) AF: 0.457 AC: 1574 AN: 3446

South Asian (SAS) AF: 0.304 AC: 792 AN: 2604

European-Finnish (FIN) AF: 0.214 AC: 1256 AN: 5867

Middle Eastern (MID) AF: 0.186 AC: 40 AN: 215

European-Non Finnish (NFE) AF: 0.172 AC: 9074 AN: 52647

Other (OTH) AF: 0.256 AC: 385 AN: 1503

Alfa AF: 0.214 Hom.: 2078

Bravo AF: 0.299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.7
DANN	Benign	0.76
PhyloP100		-0.086
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: rs6627221; hg19: chrX-151415874;