Genetic Variant GABRA4:c.87-10delT (chr4-46992955-GA-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000809.4(GABRA4):c.87-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 903 hom., cov: 0)

Exomes 𝑓: 0.11 ( 1958 hom. )

Consequence

GABRA4
NM_000809.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0260

Publications

1 publications found

Variant links:

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

GABRA4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GABRA4	NM_000809.4 link	c.87-10delT	intron_variant	Intron 1 of 8	ENST00000264318.4	NP_000800.2	P48169X5D7F5
GABRA4	NM_001204266.2 link	c.30-10delT	intron_variant	Intron 1 of 8		NP_001191195.1	P48169
GABRA4	NM_001204267.2 link	c.30-10delT	intron_variant	Intron 1 of 7		NP_001191196.1	P48169

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA4	ENST00000264318.4 link	c.87-10delT		intron_variant	Intron 1 of 8	1	NM_000809.4	ENSP00000264318.3		P48169

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

15740

AN:

144020

Hom.:

898

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.0345

Gnomad AMR

AF:

0.0875

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.0977

Gnomad OTH

AF:

0.104

GnomAD2 exomes

AF:

0.157

AC:

27110

AN:

172330

AF XY:

0.161

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.135

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.115

AC:

128771

AN:

1123876

Hom.:

1958

Cov.:

AF XY:

0.117

AC XY:

66679

AN XY:

567730

show subpopulations

African (AFR)

AF:

0.137

AC:

3518

AN:

25596

American (AMR)

AF:

0.0951

AC:

3315

AN:

34876

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

3156

AN:

21976

East Asian (EAS)

AF:

0.150

AC:

5192

AN:

34634

South Asian (SAS)

AF:

0.188

AC:

13489

AN:

71586

European-Finnish (FIN)

AF:

0.134

AC:

5893

AN:

43910

Middle Eastern (MID)

AF:

0.0978

AC:

454

AN:

4644

European-Non Finnish (NFE)

AF:

0.105

AC:

88221

AN:

838816

Other (OTH)

AF:

0.116

AC:

5533

AN:

47838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

4996

9992

14987

19983

24979

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.109

AC:

15750

AN:

144074

Hom.:

903

Cov.:

AF XY:

0.112

AC XY:

7775

AN XY:

69700

show subpopulations

African (AFR)

AF:

0.126

AC:

4936

AN:

39172

American (AMR)

AF:

0.0874

AC:

1273

AN:

14570

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

429

AN:

3410

East Asian (EAS)

AF:

0.111

AC:

543

AN:

4890

South Asian (SAS)

AF:

0.198

AC:

884

AN:

4458

European-Finnish (FIN)

AF:

0.114

AC:

970

AN:

8518

Middle Eastern (MID)

AF:

0.116

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0977

AC:

6442

AN:

65908

Other (OTH)

AF:

0.105

AC:

210

AN:

1994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

691

1381

2072

2762

3453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0876

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.026

Mutation Taster

=100/0

polymorphism (auto)

(source)

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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4-46992955-GAAAA-GAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over