4-46992955-GAA-GAAA

Position:

• chr4-46992955-GAA-GAAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000809.4(GABRA4):​c.87-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (7443 hom., cov: 0)
  • Exomes 𝑓: 0.34 (10842 hom.)
  • Failed GnomAD Quality Control
• Consequence: GABRA4 NM_000809.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0260

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-46992955-G-GA is Benign according to our data. Variant chr4-46992955-G-GA is described in ClinVar as [Benign]. Clinvar id is 402889.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA4	NM_000809.4	c.87-10dupT		intron_variant		ENST00000264318.4	NP_000800.2
GABRA4	NM_001204266.2	c.30-10dupT		intron_variant			NP_001191195.1
GABRA4	NM_001204267.2	c.30-10dupT		intron_variant			NP_001191196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA4	ENST00000264318.4	c.87-10dupT		intron_variant		1	NM_000809.4	ENSP00000264318.3

Frequencies

GnomAD3 genomes AF: 0.322 AC: 46381 AN: 143904 Hom.: 7447 Cov.: 0

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.337

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.344 AC: 371495 AN: 1079110 Hom.: 10842 Cov.: 19 AF XY: 0.344 AC XY: 186642 AN XY: 543316

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.350

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.336

Gnomad4 SAS exome AF: 0.283

Gnomad4 FIN exome AF: 0.291

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.352

GnomAD4 genome AF: 0.322 AC: 46393 AN: 143958 Hom.: 7443 Cov.: 0 AF XY: 0.312 AC XY: 21751 AN XY: 69624

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.338

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs3215202; hg19: chr4-46994972;