rs10517173

chr4-46980479-A-C

Variant summary

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

The NM_000809.4(GABRA4):c.206-1381T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,048 control chromosomes in the GnomAD database, including 915 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 0.11 (915 hom., cov: 32)
• Consequence: GABRA4 NM_000809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA4	NM_000809.4	c.206-1381T>G		intron_variant		ENST00000264318.4
GABRA4	NM_001204266.2	c.149-1381T>G		intron_variant
GABRA4	NM_001204267.2	c.149-1381T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA4	ENST00000264318.4	c.206-1381T>G		intron_variant		1	NM_000809.4	P1
GABRA4	ENST00000502874.1	c.87-1381T>G		intron_variant, NMD_transcript_variant		5
GABRA4	ENST00000508560.5	c.*27-1381T>G		intron_variant, NMD_transcript_variant		3
GABRA4	ENST00000511523.5	c.*27-1381T>G		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15983 AN: 151934 Hom.: 912 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0843

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0962

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.0970

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.0999

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

GnomAD4 genome AF: 0.105 AC: 15995 AN: 152048 Hom.: 915 Cov.: 32 AF XY: 0.106 AC XY: 7888 AN XY: 74304

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0842

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.0964

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.0970

Gnomad4 NFE AF: 0.0957

Gnomad4 OTH AF: 0.101

Alfa AF: 0.104 Hom.: 169

Bravo AF: 0.101

Asia WGS AF: 0.142 AC: 493 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	5.7
Dann	Benign	0.80

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: rs10517173; hg19: chr4-46982496;