rs530329

Variant names:

• chr4-46279102-C-T
• rs530329
• NM_000807.4:c.857-16974G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000807.4(GABRA2):​c.857-16974G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 151,824 control chromosomes in the GnomAD database, including 29,053 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 0.61 (29053 hom., cov: 32)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 3 publications found

Genes affected

GABRA2 (HGNC:4076): (gamma-aminobutyric acid type A receptor subunit alpha2) 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

GABRA2 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 78

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000807.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA2	NM_000807.4	MANE Select	c.857-16974G>A		intron	N/A	NP_000798.2
	GABRA2	NM_001330690.2		c.857-16974G>A		intron	N/A	NP_001317619.1
	GABRA2	NM_001377144.1		c.857-16974G>A		intron	N/A	NP_001364073.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA2	ENST00000381620.9	TSL:1 MANE Select	c.857-16974G>A		intron	N/A	ENSP00000371033.4
	GABRA2	ENST00000515082.5	TSL:1	c.857-16974G>A		intron	N/A	ENSP00000423840.1
	GABRA2	ENST00000507069.5	TSL:3	c.857-16974G>A		intron	N/A	ENSP00000427603.1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93052 AN: 151706 Hom.: 29027 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.613 AC: 93117 AN: 151824 Hom.: 29053 Cov.: 32 AF XY: 0.613 AC XY: 45448 AN XY: 74146

African (AFR) AF: 0.707 AC: 29308 AN: 41478

American (AMR) AF: 0.549 AC: 8366 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2413 AN: 3470

East Asian (EAS) AF: 0.495 AC: 2549 AN: 5150

South Asian (SAS) AF: 0.758 AC: 3651 AN: 4816

European-Finnish (FIN) AF: 0.586 AC: 6159 AN: 10502

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.569 AC: 38618 AN: 67878

Other (OTH) AF: 0.622 AC: 1303 AN: 2096

Alfa AF: 0.589 Hom.: 9099

Bravo AF: 0.607

Asia WGS AF: 0.632 AC: 2198 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.45
PhyloP100		0.15
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

Other links and lift over

dbSNP: rs530329; hg19: chr4-46281119;