rs526752

Variant names:

• chr4-46274612-G-A
• rs526752
• NM_000807.4:c.857-12484C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-46274612-G-A
• chr4-46274612-G-C

Variant summary

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

The NM_001330690.2(GABRA2):​c.857-12484C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,786 control chromosomes in the GnomAD database, including 29,167 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 (29167 hom., cov: 31)
• Consequence: GABRA2 NM_001330690.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.593
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330690.2. 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.857-12484C>T		intron	N/A	NP_000798.2
	GABRA2	NM_001330690.2		c.857-12484C>T		intron	N/A	NP_001317619.1
	GABRA2	NM_001377144.1		c.857-12484C>T		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.857-12484C>T		intron	N/A	ENSP00000371033.4
	GABRA2	ENST00000515082.5	TSL:1	c.857-12484C>T		intron	N/A	ENSP00000423840.1
	GABRA2	ENST00000507069.5	TSL:3	c.857-12484C>T		intron	N/A	ENSP00000427603.1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93232 AN: 151668 Hom.: 29143 Cov.: 31

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.615 AC: 93294 AN: 151786 Hom.: 29167 Cov.: 31 AF XY: 0.614 AC XY: 45543 AN XY: 74154

African (AFR) AF: 0.705 AC: 29217 AN: 41424

American (AMR) AF: 0.548 AC: 8341 AN: 15208

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

East Asian (EAS) AF: 0.549 AC: 2810 AN: 5120

South Asian (SAS) AF: 0.762 AC: 3667 AN: 4810

European-Finnish (FIN) AF: 0.584 AC: 6157 AN: 10542

Middle Eastern (MID) AF: 0.630 AC: 184 AN: 292

European-Non Finnish (NFE) AF: 0.569 AC: 38631 AN: 67908

Other (OTH) AF: 0.623 AC: 1311 AN: 2104

Alfa AF: 0.587 Hom.: 5636

Bravo AF: 0.609

Asia WGS AF: 0.650 AC: 2263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.98
DANN	Benign	0.51
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs526752; hg19: chr4-46276629;