rs7678338

chr4-46920090-T-C

Variant summary

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

The NM_000809.4(GABRA4):c.*8135A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,474 control chromosomes in the GnomAD database, including 4,662 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 0.24 (4662 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GABRA4 NM_000809.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA4	NM_000809.4	c.*8135A>G		3_prime_UTR_variant	9/9	ENST00000264318.4
GABRA4	NM_001204266.2	c.*8135A>G		3_prime_UTR_variant	9/9
GABRA4	NM_001204267.2	c.*8135A>G		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA4	ENST00000264318.4	c.*8135A>G		3_prime_UTR_variant	9/9	1	NM_000809.4	P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36767 AN: 151356 Hom.: 4664 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.250

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.243 AC: 36777 AN: 151474 Hom.: 4662 Cov.: 32 AF XY: 0.235 AC XY: 17408 AN XY: 74022

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.248

Alfa AF: 0.272 Hom.: 5683

Bravo AF: 0.243

Asia WGS AF: 0.205 AC: 710 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.91
Dann	Benign	0.77

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: rs7678338; hg19: chr4-46922107;