rs7660336

Positions:

• chr4-46927651-G-C
• chr4-46927651-G-T

Variant summary

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

The NM_000809.4(GABRA4):​c.*574C>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 0.521 in 152,320 control chromosomes in the GnomAD database, including 20,804 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 0.52 (20751 hom., cov: 32)
  • Exomes 𝑓: 0.51 (53 hom.)
• Consequence: GABRA4 NM_000809.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA4	NM_000809.4	c.*574C>G		3_prime_UTR_variant	9/9	ENST00000264318.4	NP_000800.2
GABRA4	NM_001204266.2	c.*574C>G		3_prime_UTR_variant	9/9		NP_001191195.1
GABRA4	NM_001204267.2	c.*574C>G		3_prime_UTR_variant	8/8		NP_001191196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA4	ENST00000264318	c.*574C>G		3_prime_UTR_variant	9/9	1	NM_000809.4	ENSP00000264318.3

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78970 AN: 151758 Hom.: 20717 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.503

GnomAD4 exome AF: 0.514 AC: 228 AN: 444 Hom.: 53 Cov.: 0 AF XY: 0.507 AC XY: 139 AN XY: 274

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.535

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.521 AC: 79061 AN: 151876 Hom.: 20751 Cov.: 32 AF XY: 0.521 AC XY: 38668 AN XY: 74230

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.505

Alfa AF: 0.402 Hom.: 1087

Bravo AF: 0.519

Asia WGS AF: 0.591 AC: 2051 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.51
DANN	Benign	0.62

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: rs7660336; hg19: chr4-46929668;