6-89311822-G-A

Variant names:

• chr6-89311822-G-A
• rs10944441
• NM_002043.5:c.113+3231C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002043.5(GABRR2):​c.113+3231C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,074 control chromosomes in the GnomAD database, including 3,665 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 0.22 (3665 hom., cov: 32)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 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.113+3231C>T		intron	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.113+3231C>T		intron	N/A	ENSP00000386029.4
	GABRR2	ENST00000602808.1	TSL:3	n.247+3231C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32681 AN: 151956 Hom.: 3664 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.215 AC: 32703 AN: 152074 Hom.: 3665 Cov.: 32 AF XY: 0.218 AC XY: 16183 AN XY: 74330

African (AFR) AF: 0.286 AC: 11854 AN: 41464

American (AMR) AF: 0.209 AC: 3191 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 821 AN: 3468

East Asian (EAS) AF: 0.191 AC: 982 AN: 5148

South Asian (SAS) AF: 0.259 AC: 1248 AN: 4824

European-Finnish (FIN) AF: 0.168 AC: 1776 AN: 10570

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12063 AN: 67998

Other (OTH) AF: 0.214 AC: 452 AN: 2112

Alfa AF: 0.196 Hom.: 369

Bravo AF: 0.219

Asia WGS AF: 0.238 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.012
DANN	Benign	0.73
PhyloP100		-3.0
Mutation Taster		=100/0	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: rs10944441; hg19: chr6-90021541;