chr6-89254573-G-A

Variant names:

• chr6-89254573-G-A
• rs3734198
• NM_002043.5:c.*3097C>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.*3097C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 152,076 control chromosomes in the GnomAD database, including 29,432 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 0.60 (29432 hom., cov: 32)
• Consequence: GABRR2 NM_002043.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR2	NM_002043.5	c.*3097C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000402938.4	NP_002034.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4	c.*3097C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_002043.5	ENSP00000386029.4

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91452 AN: 151958 Hom.: 29390 Cov.: 32

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.602 AC: 91538 AN: 152076 Hom.: 29432 Cov.: 32 AF XY: 0.592 AC XY: 43999 AN XY: 74316

African (AFR) AF: 0.813 AC: 33743 AN: 41484

American (AMR) AF: 0.406 AC: 6208 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1598 AN: 3466

East Asian (EAS) AF: 0.165 AC: 857 AN: 5192

South Asian (SAS) AF: 0.467 AC: 2252 AN: 4824

European-Finnish (FIN) AF: 0.553 AC: 5833 AN: 10546

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39192 AN: 67974

Other (OTH) AF: 0.553 AC: 1167 AN: 2112

Alfa AF: 0.585 Hom.: 59666

Bravo AF: 0.598

Asia WGS AF: 0.378 AC: 1318 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	1.1
DANN	Benign	0.21
PhyloP100		0.13

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3734198; hg19: chr6-89964292;