rs452667

Positions:

• chr6-89193601-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRR1	NM_002042.5	c.573-3354G>A		intron_variant		ENST00000454853.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRR1	ENST00000454853.7	c.573-3354G>A		intron_variant		1	NM_002042.5	P1
GABRR1	ENST00000369451.7	c.312-3354G>A		intron_variant		5
GABRR1	ENST00000435811.5	c.522-3354G>A		intron_variant		2
GABRR1	ENST00000457434.1	c.*534-3354G>A		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.223

Alfa AF: 0.204 Hom.: 1523

Bravo AF: 0.245

Asia WGS AF: 0.231 AC: 801 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.12
DANN	Benign	0.77

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: rs452667; hg19: chr6-89903320;