rs3792208

Variant names:

• chr4-46972021-C-A
• rs3792208
• NM_000809.4:c.722-786G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000809.4(GABRA4):​c.722-786G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0987 in 151,498 control chromosomes in the GnomAD database, including 869 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 0.099 (869 hom., cov: 32)
• Consequence: GABRA4 NM_000809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA4	NM_000809.4	c.722-786G>T		intron_variant	Intron 6 of 8	ENST00000264318.4	NP_000800.2
GABRA4	NM_001204266.2	c.665-786G>T		intron_variant	Intron 6 of 8		NP_001191195.1
GABRA4	NM_001204267.2	c.664+2211G>T		intron_variant	Intron 6 of 7		NP_001191196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA4	ENST00000264318.4	c.722-786G>T		intron_variant	Intron 6 of 8	1	NM_000809.4	ENSP00000264318.3
GABRA4	ENST00000502874.1	n.*492-786G>T		intron_variant	Intron 5 of 5	5		ENSP00000424386.1
GABRA4	ENST00000508560.5	n.*543-786G>T		intron_variant	Intron 6 of 8	3		ENSP00000425445.1
GABRA4	ENST00000511523.5	n.*542+2211G>T		intron_variant	Intron 6 of 7	3		ENSP00000422152.1

Frequencies

GnomAD3 genomes AF: 0.0988 AC: 14950 AN: 151380 Hom.: 867 Cov.: 32

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0678

Gnomad ASJ AF: 0.0566

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0729

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

GnomAD4 genome AF: 0.0987 AC: 14959 AN: 151498 Hom.: 869 Cov.: 32 AF XY: 0.100 AC XY: 7415 AN XY: 74032

African (AFR) AF: 0.0857 AC: 3550 AN: 41446

American (AMR) AF: 0.0677 AC: 1025 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.0566 AC: 196 AN: 3460

East Asian (EAS) AF: 0.107 AC: 548 AN: 5128

South Asian (SAS) AF: 0.235 AC: 1134 AN: 4818

European-Finnish (FIN) AF: 0.132 AC: 1396 AN: 10562

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6909 AN: 67630

Other (OTH) AF: 0.0755 AC: 159 AN: 2106

Alfa AF: 0.0940 Hom.: 1284

Bravo AF: 0.0882

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.68
PhyloP100		-0.12
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

Publications

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Other links and lift over

dbSNP: rs3792208; hg19: chr4-46974038;