rs507788

Variant names:

• chr4-46255441-C-T
• rs507788
• NM_000807.4:c.1060-4837G>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.1060-4837G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 151,222 control chromosomes in the GnomAD database, including 27,966 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 0.60 (27966 hom., cov: 31)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA2	NM_000807.4	c.1060-4837G>A		intron_variant	Intron 9 of 9	ENST00000381620.9	NP_000798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000381620.9	c.1060-4837G>A		intron_variant	Intron 9 of 9	1	NM_000807.4	ENSP00000371033.4

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91201 AN: 151104 Hom.: 27960 Cov.: 31

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.603 AC: 91229 AN: 151222 Hom.: 27966 Cov.: 31 AF XY: 0.603 AC XY: 44500 AN XY: 73834

African (AFR) AF: 0.679 AC: 28061 AN: 41340

American (AMR) AF: 0.543 AC: 8211 AN: 15118

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2393 AN: 3452

East Asian (EAS) AF: 0.549 AC: 2785 AN: 5074

South Asian (SAS) AF: 0.759 AC: 3655 AN: 4818

European-Finnish (FIN) AF: 0.572 AC: 6020 AN: 10516

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38076 AN: 67606

Other (OTH) AF: 0.611 AC: 1280 AN: 2094

Alfa AF: 0.576 Hom.: 3182

Bravo AF: 0.598

Asia WGS AF: 0.635 AC: 2196 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.25
PhyloP100		-0.33
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: rs507788; hg19: chr4-46257458;