6-89193601-C-T

Variant names:

• chr6-89193601-C-T
• rs452667
• NM_002042.5:c.573-3354G>A

Variant summary

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

The NM_002042.5(GABRR1):​c.573-3354G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,010 control chromosomes in the GnomAD database, including 4,281 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 0.23 (4281 hom., cov: 31)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.924
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002042.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR1	NM_002042.5	MANE Select	c.573-3354G>A		intron	N/A	NP_002033.2	P24046-1
	GABRR1	NM_001256703.1		c.522-3354G>A		intron	N/A	NP_001243632.1	P24046-2
	GABRR1	NM_001256704.1		c.312-3354G>A		intron	N/A	NP_001243633.1	P24046-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR1	ENST00000454853.7	TSL:1 MANE Select	c.573-3354G>A		intron	N/A	ENSP00000412673.2	P24046-1
	GABRR1	ENST00000435811.5	TSL:2	c.522-3354G>A		intron	N/A	ENSP00000394687.1	P24046-2
	GABRR1	ENST00000369451.7	TSL:5	c.312-3354G>A		intron	N/A	ENSP00000358463.3	P24046-3

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35088 AN: 151892 Hom.: 4269 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.231 AC: 35150 AN: 152010 Hom.: 4281 Cov.: 31 AF XY: 0.229 AC XY: 17030 AN XY: 74290

African (AFR) AF: 0.290 AC: 12033 AN: 41448

American (AMR) AF: 0.288 AC: 4388 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 775 AN: 3466

East Asian (EAS) AF: 0.207 AC: 1071 AN: 5176

South Asian (SAS) AF: 0.220 AC: 1059 AN: 4806

European-Finnish (FIN) AF: 0.201 AC: 2125 AN: 10566

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12995 AN: 67976

Other (OTH) AF: 0.223 AC: 472 AN: 2116

Alfa AF: 0.204 Hom.: 1700

Bravo AF: 0.245

Asia WGS AF: 0.231 AC: 801 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.12
DANN	Benign	0.77
PhyloP100		-0.92
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: rs452667; hg19: chr6-89903320;