4-46992955-GAA-GA

Position:

• chr4-46992955-GAA-GA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000809.4(GABRA4):​c.87-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (903 hom., cov: 0)
  • Exomes 𝑓: 0.11 (1958 hom.)
• Consequence: GABRA4 NM_000809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

Genes affected

GABRA4 (HGNC:4078): (gamma-aminobutyric acid type A receptor subunit alpha4) Gamma-aminobutyric acid (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. This gene encodes subunit alpha-4, which is involved in the etiology of autism and eventually increases autism risk through interaction with another subunit, gamma-aminobutyric acid receptor beta-1 (GABRB1). Alternatively spliced transcript variants encoding different isoforms have been found in this gene.[provided by RefSeq, Feb 2011]

GABRA4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA4	NM_000809.4	c.87-10delT		intron_variant		ENST00000264318.4	NP_000800.2
GABRA4	NM_001204266.2	c.30-10delT		intron_variant			NP_001191195.1
GABRA4	NM_001204267.2	c.30-10delT		intron_variant			NP_001191196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA4	ENST00000264318.4	c.87-10delT		intron_variant		1	NM_000809.4	ENSP00000264318.3

Frequencies

GnomAD3 genomes AF: 0.109 AC: 15740 AN: 144020 Hom.: 898 Cov.: 0

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0345

Gnomad AMR AF: 0.0875

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0977

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.115 AC: 128771 AN: 1123876 Hom.: 1958 Cov.: 19 AF XY: 0.117 AC XY: 66679 AN XY: 567730

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.0951

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.109 AC: 15750 AN: 144074 Hom.: 903 Cov.: 0 AF XY: 0.112 AC XY: 7775 AN XY: 69700

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0874

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0977

Gnomad4 OTH AF: 0.105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3215202; hg19: chr4-46994972;