4-46992955-GAA-GAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_000809.4(GABRA4):​c.87-11_87-10dupTT 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 0.014 ( 25 hom., cov: 0)
Exomes 𝑓: 0.029 ( 26 hom. )

Consequence

GABRA4
NM_000809.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0260
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0142 (2053/144080) while in subpopulation EAS AF= 0.0405 (198/4890). AF 95% confidence interval is 0.0359. There are 25 homozygotes in gnomad4. There are 978 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High AC in GnomAd4 at 2053 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GABRA4NM_000809.4 linkuse as main transcriptc.87-11_87-10dupTT intron_variant ENST00000264318.4 NP_000800.2 P48169X5D7F5
GABRA4NM_001204266.2 linkuse as main transcriptc.30-11_30-10dupTT intron_variant NP_001191195.1 P48169
GABRA4NM_001204267.2 linkuse as main transcriptc.30-11_30-10dupTT intron_variant NP_001191196.1 P48169

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GABRA4ENST00000264318.4 linkuse as main transcriptc.87-10_87-9insTT intron_variant 1 NM_000809.4 ENSP00000264318.3 P48169

Frequencies

GnomAD3 genomes
AF:
0.0142
AC:
2043
AN:
144024
Hom.:
24
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0168
Gnomad AMI
AF:
0.00920
Gnomad AMR
AF:
0.0140
Gnomad ASJ
AF:
0.00381
Gnomad EAS
AF:
0.0406
Gnomad SAS
AF:
0.00624
Gnomad FIN
AF:
0.0106
Gnomad MID
AF:
0.00327
Gnomad NFE
AF:
0.0123
Gnomad OTH
AF:
0.0162
GnomAD4 exome
AF:
0.0290
AC:
32859
AN:
1133516
Hom.:
26
Cov.:
19
AF XY:
0.0283
AC XY:
16241
AN XY:
573028
show subpopulations
Gnomad4 AFR exome
AF:
0.0281
Gnomad4 AMR exome
AF:
0.0195
Gnomad4 ASJ exome
AF:
0.0260
Gnomad4 EAS exome
AF:
0.0519
Gnomad4 SAS exome
AF:
0.0143
Gnomad4 FIN exome
AF:
0.0168
Gnomad4 NFE exome
AF:
0.0305
Gnomad4 OTH exome
AF:
0.0288
GnomAD4 genome
AF:
0.0142
AC:
2053
AN:
144080
Hom.:
25
Cov.:
0
AF XY:
0.0140
AC XY:
978
AN XY:
69690
show subpopulations
Gnomad4 AFR
AF:
0.0171
Gnomad4 AMR
AF:
0.0139
Gnomad4 ASJ
AF:
0.00381
Gnomad4 EAS
AF:
0.0405
Gnomad4 SAS
AF:
0.00627
Gnomad4 FIN
AF:
0.0106
Gnomad4 NFE
AF:
0.0123
Gnomad4 OTH
AF:
0.0155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3215202; hg19: chr4-46994972; API