X-152449531-G-C

Variant names:

• chrX-152449531-G-C
• rs6627595
• NM_000808.4:c.-27+1615C>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.-27+1615C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 110,271 control chromosomes in the GnomAD database, including 6,848 homozygotes. There are 13,308 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 0.41 (6848 hom., 13308 hem., cov: 22)
• Consequence: GABRA3 NM_000808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA3	NM_000808.4	c.-27+1615C>G		intron_variant	Intron 1 of 9	ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4	c.-27+1615C>G		intron_variant	Intron 1 of 8		XP_006724874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA3	ENST00000370314.9	c.-27+1615C>G		intron_variant	Intron 1 of 9	1	NM_000808.4	ENSP00000359337.4

Frequencies

GnomAD3 genomes AF: 0.413 AC: 45536 AN: 110216 Hom.: 6846 Cov.: 22

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.413 AC: 45559 AN: 110271 Hom.: 6848 Cov.: 22 AF XY: 0.408 AC XY: 13308 AN XY: 32597

African (AFR) AF: 0.418 AC: 12633 AN: 30243

American (AMR) AF: 0.507 AC: 5258 AN: 10366

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1246 AN: 2622

East Asian (EAS) AF: 0.645 AC: 2234 AN: 3463

South Asian (SAS) AF: 0.410 AC: 1060 AN: 2583

European-Finnish (FIN) AF: 0.338 AC: 1967 AN: 5813

Middle Eastern (MID) AF: 0.452 AC: 95 AN: 210

European-Non Finnish (NFE) AF: 0.384 AC: 20290 AN: 52795

Other (OTH) AF: 0.419 AC: 628 AN: 1500

Alfa AF: 0.219 Hom.: 1000

Bravo AF: 0.430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.52
DANN	Benign	0.48
PhyloP100		-0.27
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: rs6627595; hg19: chrX-151618003;