rs3792211

Variant names:

• chr4-46992478-C-A
• rs3792211
• NM_000809.4:c.205+350G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-46992478-C-A
• chr4-46992478-C-G
• chr4-46992478-C-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.205+350G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 151,970 control chromosomes in the GnomAD database, including 6,256 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 0.28 (6256 hom., cov: 31)
• Consequence: GABRA4 NM_000809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Illumina

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000809.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA4	NM_000809.4	MANE Select	c.205+350G>T		intron	N/A	NP_000800.2
	GABRA4	NM_001204266.2		c.148+350G>T		intron	N/A	NP_001191195.1
	GABRA4	NM_001204267.2		c.148+350G>T		intron	N/A	NP_001191196.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA4	ENST00000264318.4	TSL:1 MANE Select	c.205+350G>T		intron	N/A	ENSP00000264318.3
	GABRA4	ENST00000502874.1	TSL:5	n.86+861G>T		intron	N/A	ENSP00000424386.1
	GABRA4	ENST00000508560.5	TSL:3	n.*26+350G>T		intron	N/A	ENSP00000425445.1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42140 AN: 151850 Hom.: 6255 Cov.: 31

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.277 AC: 42160 AN: 151970 Hom.: 6256 Cov.: 31 AF XY: 0.267 AC XY: 19841 AN XY: 74286

African (AFR) AF: 0.212 AC: 8799 AN: 41430

American (AMR) AF: 0.255 AC: 3889 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1255 AN: 3470

East Asian (EAS) AF: 0.351 AC: 1808 AN: 5156

South Asian (SAS) AF: 0.171 AC: 826 AN: 4820

European-Finnish (FIN) AF: 0.180 AC: 1902 AN: 10580

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.334 AC: 22675 AN: 67934

Other (OTH) AF: 0.300 AC: 633 AN: 2112

Alfa AF: 0.303 Hom.: 4877

Bravo AF: 0.282

Asia WGS AF: 0.237 AC: 824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.3
DANN	Benign	0.82
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3792211; hg19: chr4-46994495;