NM_002042.5:c.*46A>G

Variant names:

• chr6-89178724-T-C
• rs3734201
• NM_002042.5:c.*46A>G

Variant summary

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

The NM_002042.5(GABRR1):​c.*46A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,500,802 control chromosomes in the GnomAD database, including 133,001 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 0.42 (13673 hom., cov: 32)
  • Exomes 𝑓: 0.42 (119328 hom.)
• Consequence: GABRR1 NM_002042.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 11 publications found

Genes affected

GABRR1 (HGNC:4090): (gamma-aminobutyric acid type A receptor subunit rho1) GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. GABRR1 is a member of the rho subunit family. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR1	NM_002042.5	c.*46A>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000454853.7	NP_002033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000454853.7	c.*46A>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_002042.5	ENSP00000412673.2
GABRR1	ENST00000435811.5	c.*46A>G		3_prime_UTR_variant	Exon 9 of 9	2		ENSP00000394687.1
GABRR1	ENST00000369451.7	c.*46A>G		3_prime_UTR_variant	Exon 12 of 12	5		ENSP00000358463.3
GABRR1	ENST00000457434.1	n.*1447A>G		downstream_gene_variant		5		ENSP00000410130.1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63891 AN: 151850 Hom.: 13641 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.440

GnomAD2 exomes AF: 0.411 AC: 100920 AN: 245522 AF XY: 0.411

Gnomad AFR exome AF: 0.450

Gnomad AMR exome AF: 0.480

Gnomad ASJ exome AF: 0.435

Gnomad EAS exome AF: 0.241

Gnomad FIN exome AF: 0.319

Gnomad NFE exome AF: 0.424

Gnomad OTH exome AF: 0.428

GnomAD4 exome AF: 0.417 AC: 563083 AN: 1348834 Hom.: 119328 Cov.: 20 AF XY: 0.418 AC XY: 281996 AN XY: 675040

African (AFR) AF: 0.457 AC: 14164 AN: 31020

American (AMR) AF: 0.477 AC: 20977 AN: 43944

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 10922 AN: 25204

East Asian (EAS) AF: 0.230 AC: 8966 AN: 39008

South Asian (SAS) AF: 0.417 AC: 34871 AN: 83540

European-Finnish (FIN) AF: 0.319 AC: 16482 AN: 51722

Middle Eastern (MID) AF: 0.434 AC: 2306 AN: 5316

European-Non Finnish (NFE) AF: 0.425 AC: 430535 AN: 1012628

Other (OTH) AF: 0.423 AC: 23860 AN: 56452

GnomAD4 genome AF: 0.421 AC: 63977 AN: 151968 Hom.: 13673 Cov.: 32 AF XY: 0.411 AC XY: 30557 AN XY: 74282

African (AFR) AF: 0.453 AC: 18778 AN: 41428

American (AMR) AF: 0.445 AC: 6788 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1476 AN: 3470

East Asian (EAS) AF: 0.247 AC: 1277 AN: 5180

South Asian (SAS) AF: 0.409 AC: 1962 AN: 4802

European-Finnish (FIN) AF: 0.314 AC: 3320 AN: 10564

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28917 AN: 67950

Other (OTH) AF: 0.444 AC: 937 AN: 2112

Alfa AF: 0.430 Hom.: 39684

Bravo AF: 0.435

Asia WGS AF: 0.383 AC: 1334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.76
PhyloP100		0.077
Mutation Taster		=99/1	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: rs3734201; hg19: chr6-89888443; COSMIC: COSV65619222; COSMIC: COSV65619222;