rs548260

Variant names:

• chr4-46266467-G-A
• rs548260
• NM_000807.4:c.857-4339C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-46266467-G-A
• chr4-46266467-G-C
• chr4-46266467-G-T

Variant summary

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

The NM_000807.4(GABRA2):​c.857-4339C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 149,690 control chromosomes in the GnomAD database, including 30,093 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 0.63 (30093 hom., cov: 29)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.744 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.857-4339C>T		intron	N/A	NP_000798.2
	GABRA2	NM_001330690.2		c.857-4339C>T		intron	N/A	NP_001317619.1
	GABRA2	NM_001377144.1		c.857-4339C>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.857-4339C>T		intron	N/A	ENSP00000371033.4
	GABRA2	ENST00000515082.5	TSL:1	c.857-4339C>T		intron	N/A	ENSP00000423840.1
	GABRA2	ENST00000507069.5	TSL:3	c.857-4339C>T		intron	N/A	ENSP00000427603.1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 93797 AN: 149622 Hom.: 30066 Cov.: 29

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.641

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.627 AC: 93845 AN: 149690 Hom.: 30093 Cov.: 29 AF XY: 0.627 AC XY: 45759 AN XY: 73012

African (AFR) AF: 0.747 AC: 30703 AN: 41090

American (AMR) AF: 0.552 AC: 8283 AN: 14996

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2398 AN: 3450

East Asian (EAS) AF: 0.548 AC: 2785 AN: 5078

South Asian (SAS) AF: 0.764 AC: 3643 AN: 4766

European-Finnish (FIN) AF: 0.583 AC: 5569 AN: 9552

Middle Eastern (MID) AF: 0.625 AC: 180 AN: 288

European-Non Finnish (NFE) AF: 0.569 AC: 38402 AN: 67476

Other (OTH) AF: 0.633 AC: 1321 AN: 2086

Alfa AF: 0.584 Hom.: 5189

Bravo AF: 0.623

Asia WGS AF: 0.654 AC: 2270 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.86
DANN	Benign	0.13
PhyloP100		-0.67
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: rs548260; hg19: chr4-46268484;