6-89284979-C-G

Position:

• chr6-89284979-C-G

Variant summary

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

The NM_002043.5(GABRR2):​c.221-13257G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,118 control chromosomes in the GnomAD database, including 5,952 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 0.28 (5952 hom., cov: 32)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157

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]

GABRR2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRR2	NM_002043.5	c.221-13257G>C		intron_variant		ENST00000402938.4	NP_002034.3
GABRR2	XM_047418599.1	c.296-13257G>C		intron_variant			XP_047274555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4	c.221-13257G>C		intron_variant		1	NM_002043.5	ENSP00000386029.4
GABRR2	ENST00000602808.1	n.355-13257G>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41859 AN: 152000 Hom.: 5940 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.275 AC: 41900 AN: 152118 Hom.: 5952 Cov.: 32 AF XY: 0.281 AC XY: 20895 AN XY: 74354

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.286

Alfa AF: 0.282 Hom.: 770

Bravo AF: 0.269

Asia WGS AF: 0.279 AC: 973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.57

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: rs9362632; hg19: chr6-89994698;