rs10944441

chr6-89311822-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRR2	NM_002043.5	c.113+3231C>T		intron_variant		ENST00000402938.4
GABRR2	XM_047418599.1	c.188+3231C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRR2	ENST00000402938.4	c.113+3231C>T		intron_variant		1	NM_002043.5	P1
GABRR2	ENST00000602808.1	n.247+3231C>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.214

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.012
Dann	Benign	0.73

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: rs10944441; hg19: chr6-90021541;