rs282129

Variant names:

• chr6-89257779-G-A
• rs282129
• NM_002043.5:c.1289C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-89257779-G-A
• chr6-89257779-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002043.5(GABRR2):​c.1289C>T​(p.Thr430Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,613,486 control chromosomes in the GnomAD database, including 65,810 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7447 hom., cov: 32)
  • Exomes 𝑓: 0.28 (58363 hom.)
• Consequence: GABRR2 NM_002043.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.10
• Publications: 33 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.2558393E-4).
• BP6: Variant 6-89257779-G-A is Benign according to our data. Variant chr6-89257779-G-A is described in ClinVar as Benign. ClinVar VariationId is 1286404.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR2	NM_002043.5	c.1289C>T	p.Thr430Met	missense_variant	Exon 9 of 9	ENST00000402938.4	NP_002034.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4	c.1289C>T	p.Thr430Met	missense_variant	Exon 9 of 9	1	NM_002043.5	ENSP00000386029.4
GABRR2	ENST00000602432.1	n.1120C>T		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45865 AN: 151960 Hom.: 7448 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.245

GnomAD2 exomes AF: 0.248 AC: 62126 AN: 250866 AF XY: 0.245

Gnomad AFR exome AF: 0.430

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.143

Gnomad FIN exome AF: 0.298

Gnomad NFE exome AF: 0.281

Gnomad OTH exome AF: 0.240

GnomAD4 exome AF: 0.277 AC: 405262 AN: 1461406 Hom.: 58363 Cov.: 34 AF XY: 0.274 AC XY: 199125 AN XY: 726986

African (AFR) AF: 0.436 AC: 14610 AN: 33476

American (AMR) AF: 0.155 AC: 6949 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 4538 AN: 26134

East Asian (EAS) AF: 0.130 AC: 5144 AN: 39700

South Asian (SAS) AF: 0.193 AC: 16608 AN: 86254

European-Finnish (FIN) AF: 0.298 AC: 15931 AN: 53396

Middle Eastern (MID) AF: 0.171 AC: 985 AN: 5766

European-Non Finnish (NFE) AF: 0.292 AC: 324556 AN: 1111602

Other (OTH) AF: 0.264 AC: 15941 AN: 60362

GnomAD4 genome AF: 0.302 AC: 45890 AN: 152080 Hom.: 7447 Cov.: 32 AF XY: 0.296 AC XY: 21982 AN XY: 74342

African (AFR) AF: 0.423 AC: 17545 AN: 41476

American (AMR) AF: 0.181 AC: 2765 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3470

East Asian (EAS) AF: 0.148 AC: 767 AN: 5172

South Asian (SAS) AF: 0.188 AC: 907 AN: 4816

European-Finnish (FIN) AF: 0.295 AC: 3117 AN: 10570

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19399 AN: 67970

Other (OTH) AF: 0.245 AC: 517 AN: 2114

Alfa AF: 0.282 Hom.: 28655

Bravo AF: 0.299

TwinsUK AF: 0.276 AC: 1023

ALSPAC AF: 0.288 AC: 1109

ESP6500AA AF: 0.426 AC: 1877

ESP6500EA AF: 0.279 AC: 2397

ExAC AF: 0.255 AC: 30947

Asia WGS AF: 0.186 AC: 649 AN: 3478

EpiCase AF: 0.268

EpiControl AF: 0.260

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 17, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 19536785) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.00083	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.55	N
PhyloP100		2.1
PrimateAI	Benign	0.28	T
REVEL	Benign	0.13
Sift4G	Benign	0.13	T
Vest4		0.021
MPC		0.15
ClinPred		0.010	T
GERP RS		3.5
Varity_R		0.015
gMVP		0.42
Mutation Taster		=97/3	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: rs282129; hg19: chr6-89967498; COSMIC: COSV68764405;