6-89315393-G-T

Variant names:

• chr6-89315393-G-T
• rs2236204
• NM_002043.5:c.-228C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002043.5(GABRR2):​c.-228C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 983,492 control chromosomes in the GnomAD database, including 16,493 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 0.15 (2023 hom., cov: 32)
  • Exomes 𝑓: 0.18 (14470 hom.)
• Consequence: GABRR2 NM_002043.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343
• Publications: 6 publications found

Genes affected

GABRR2 (HGNC:4091): (gamma-aminobutyric acid type A receptor subunit rho2) Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. The protein encoded by this gene is a member of the rho subunit family and is a component of the GABA type A receptor complex. This gene exists on chromosome 6q next to the gene encoding the rho 1 subunit of the GABA type A receptor, in a region thought to be associated with susceptibility for psychiatric disorders and epilepsy. Polymorphisms in this gene may also be associated with alcohol dependence, and general cognitive ability. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002043.5. 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
	GABRR2	NM_002043.5	MANE Select	c.-228C>A		upstream_gene	N/A	NP_002034.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR2	ENST00000402938.4	TSL:1 MANE Select	c.-228C>A		upstream_gene	N/A	ENSP00000386029.4
	GABRR2	ENST00000602808.1	TSL:3	n.-94C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23037 AN: 152044 Hom.: 2024 Cov.: 32

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.181 AC: 150543 AN: 831328 Hom.: 14470 AF XY: 0.184 AC XY: 76501 AN XY: 415074

African (AFR) AF: 0.0594 AC: 1149 AN: 19358

American (AMR) AF: 0.192 AC: 3676 AN: 19136

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 3183 AN: 13520

East Asian (EAS) AF: 0.207 AC: 5284 AN: 25582

South Asian (SAS) AF: 0.268 AC: 13511 AN: 50370

European-Finnish (FIN) AF: 0.169 AC: 4985 AN: 29516

Middle Eastern (MID) AF: 0.226 AC: 539 AN: 2384

European-Non Finnish (NFE) AF: 0.176 AC: 111725 AN: 636100

Other (OTH) AF: 0.184 AC: 6491 AN: 35362

GnomAD4 genome AF: 0.151 AC: 23043 AN: 152164 Hom.: 2023 Cov.: 32 AF XY: 0.156 AC XY: 11580 AN XY: 74388

African (AFR) AF: 0.0660 AC: 2742 AN: 41526

American (AMR) AF: 0.183 AC: 2793 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 819 AN: 3468

East Asian (EAS) AF: 0.190 AC: 981 AN: 5172

South Asian (SAS) AF: 0.258 AC: 1244 AN: 4824

European-Finnish (FIN) AF: 0.169 AC: 1788 AN: 10574

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11996 AN: 67996

Other (OTH) AF: 0.176 AC: 371 AN: 2112

Alfa AF: 0.167 Hom.: 6252

Bravo AF: 0.146

Asia WGS AF: 0.226 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		0.34
PromoterAI		0.020	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2236204; hg19: chr6-90025112; COSMIC: COSV68765063;