6-89296206-T-C

Variant names:

• chr6-89296206-T-C
• rs2148174
• NM_002043.5:c.220+3553A>G

Variant summary

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

The NM_002043.5(GABRR2):​c.220+3553A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,210 control chromosomes in the GnomAD database, including 40,511 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 0.73 (40511 hom., cov: 34)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• Publications: 10 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 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.220+3553A>G		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.220+3553A>G		intron	N/A	ENSP00000386029.4
	GABRR2	ENST00000602808.1	TSL:3	n.354+3553A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110571 AN: 152092 Hom.: 40482 Cov.: 34

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.727 AC: 110655 AN: 152210 Hom.: 40511 Cov.: 34 AF XY: 0.732 AC XY: 54440 AN XY: 74414

African (AFR) AF: 0.704 AC: 29247 AN: 41538

American (AMR) AF: 0.781 AC: 11947 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2581 AN: 3470

East Asian (EAS) AF: 0.977 AC: 5067 AN: 5184

South Asian (SAS) AF: 0.743 AC: 3585 AN: 4828

European-Finnish (FIN) AF: 0.750 AC: 7932 AN: 10582

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47803 AN: 67996

Other (OTH) AF: 0.746 AC: 1576 AN: 2114

Alfa AF: 0.712 Hom.: 73379

Bravo AF: 0.729

Asia WGS AF: 0.841 AC: 2922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.67
PhyloP100		-0.21
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: rs2148174; hg19: chr6-90005925;