6-89299025-C-T

Variant names:

• chr6-89299025-C-T
• rs7742664
• NM_002043.5:c.220+734G>A

Variant summary

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

The NM_002043.5(GABRR2):​c.220+734G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 151,990 control chromosomes in the GnomAD database, including 5,814 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 0.27 (5814 hom., cov: 32)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR2	NM_002043.5	c.220+734G>A		intron_variant	Intron 2 of 8	ENST00000402938.4	NP_002034.3
GABRR2	XM_047418599.1	c.295+734G>A		intron_variant	Intron 2 of 9		XP_047274555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4	c.220+734G>A		intron_variant	Intron 2 of 8	1	NM_002043.5	ENSP00000386029.4
GABRR2	ENST00000602808.1	n.354+734G>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41136 AN: 151870 Hom.: 5812 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.271 AC: 41155 AN: 151990 Hom.: 5814 Cov.: 32 AF XY: 0.276 AC XY: 20537 AN XY: 74278

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.272

Alfa AF: 0.247 Hom.: 9524

Bravo AF: 0.263

Asia WGS AF: 0.333 AC: 1159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.53

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: rs7742664; hg19: chr6-90008744;