rs6942204

Variant names:

• chr6-89306249-T-C
• rs6942204
• NM_002043.5:c.114-6384A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002043.5(GABRR2):​c.114-6384A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,554 control chromosomes in the GnomAD database, including 11,304 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 0.37 (11304 hom., cov: 30)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR2	NM_002043.5	c.114-6384A>G		intron_variant	Intron 1 of 8	ENST00000402938.4	NP_002034.3
GABRR2	XM_047418599.1	c.189-6384A>G		intron_variant	Intron 1 of 9		XP_047274555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4	c.114-6384A>G		intron_variant	Intron 1 of 8	1	NM_002043.5	ENSP00000386029.4
GABRR2	ENST00000602808.1	n.248-6384A>G		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55662 AN: 151436 Hom.: 11280 Cov.: 30

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.368 AC: 55740 AN: 151554 Hom.: 11304 Cov.: 30 AF XY: 0.373 AC XY: 27599 AN XY: 74016

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.351

Alfa AF: 0.307 Hom.: 3348

Bravo AF: 0.364

Asia WGS AF: 0.413 AC: 1436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs6942204; hg19: chr6-90015968;