rs16859788

Variant names:

• chr4-46969992-A-C
• rs16859788
• NM_000809.4:c.874+1091T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-46969992-A-C
• chr4-46969992-A-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.874+1091T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0471 in 151,202 control chromosomes in the GnomAD database, including 569 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 0.047 (569 hom., cov: 31)
• Consequence: GABRA4 NM_000809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA4	NM_000809.4	MANE Select	c.874+1091T>G		intron	N/A	NP_000800.2
	GABRA4	NM_001204266.2		c.817+1091T>G		intron	N/A	NP_001191195.1
	GABRA4	NM_001204267.2		c.664+4240T>G		intron	N/A	NP_001191196.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA4	ENST00000264318.4	TSL:1 MANE Select	c.874+1091T>G		intron	N/A	ENSP00000264318.3	P48169
	GABRA4	ENST00000900310.1		c.721+4240T>G		intron	N/A	ENSP00000570369.1
	GABRA4	ENST00000508560.5	TSL:3	n.*695+1091T>G		intron	N/A	ENSP00000425445.1	D6R924

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7110 AN: 151084 Hom.: 567 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.000870

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000624

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000711

Gnomad OTH AF: 0.0362

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

GnomAD4 genome AF: 0.0471 AC: 7118 AN: 151202 Hom.: 569 Cov.: 31 AF XY: 0.0451 AC XY: 3333 AN XY: 73904

African (AFR) AF: 0.164 AC: 6752 AN: 41296

American (AMR) AF: 0.0152 AC: 230 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.000870 AC: 3 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5108

South Asian (SAS) AF: 0.000624 AC: 3 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.000711 AC: 48 AN: 67532

Other (OTH) AF: 0.0359 AC: 75 AN: 2092

Alfa AF: 0.00934 Hom.: 4

Bravo AF: 0.0522

Asia WGS AF: 0.00867 AC: 31 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.82
PhyloP100		0.14
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs16859788;

hg19: chr4-46972009;