4-46992955-G-GAAAAAA

Variant names:

• chr4-46992955-G-GAAAAAA
• rs3215202
• NM_000809.4:c.87-15_87-10dupTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000809.4(GABRA4):​c.87-15_87-10dupTTTTTT 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: not found (cov: 0)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: GABRA4 NM_000809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.87-15_87-10dupTTTTTT		intron	N/A	NP_000800.2
	GABRA4	NM_001204266.2		c.30-15_30-10dupTTTTTT		intron	N/A	NP_001191195.1
	GABRA4	NM_001204267.2		c.30-15_30-10dupTTTTTT		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.87-10_87-9insTTTTTT		intron	N/A	ENSP00000264318.3	P48169
	GABRA4	ENST00000900310.1		c.87-10_87-9insTTTTTT		intron	N/A	ENSP00000570369.1
	GABRA4	ENST00000502874.1	TSL:5	n.86+383_86+384insTTTTTT		intron	N/A	ENSP00000424386.1	D6RB66

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 8.64e-7 AC: 1 AN: 1157260 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 585376

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26596

American (AMR) AF: 0.00 AC: 0 AN: 36862

Ashkenazi Jewish (ASJ) AF: 0.0000442 AC: 1 AN: 22628

East Asian (EAS) AF: 0.00 AC: 0 AN: 36012

South Asian (SAS) AF: 0.00 AC: 0 AN: 74638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4810

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 859184

Other (OTH) AF: 0.00 AC: 0 AN: 49366

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.026

Splicing

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: rs3215202; hg19: chr4-46994972;