rs453503

Variant names:

• chr6-89190880-C-T
• rs453503
• NM_002042.5:c.573-633G>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.573-633G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,062 control chromosomes in the GnomAD database, including 5,022 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 0.24 (5022 hom., cov: 32)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.873
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR1	NM_002042.5	c.573-633G>A		intron_variant	Intron 5 of 9	ENST00000454853.7	NP_002033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000454853.7	c.573-633G>A		intron_variant	Intron 5 of 9	1	NM_002042.5	ENSP00000412673.2
GABRR1	ENST00000435811.5	c.522-633G>A		intron_variant	Intron 4 of 8	2		ENSP00000394687.1
GABRR1	ENST00000369451.7	c.312-633G>A		intron_variant	Intron 7 of 11	5		ENSP00000358463.3
GABRR1	ENST00000457434.1	n.*534-633G>A		intron_variant	Intron 6 of 10	5		ENSP00000410130.1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37040 AN: 151944 Hom.: 5027 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.244 AC: 37055 AN: 152062 Hom.: 5022 Cov.: 32 AF XY: 0.253 AC XY: 18823 AN XY: 74308

African (AFR) AF: 0.266 AC: 11043 AN: 41500

American (AMR) AF: 0.302 AC: 4614 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 619 AN: 3466

East Asian (EAS) AF: 0.625 AC: 3228 AN: 5166

South Asian (SAS) AF: 0.293 AC: 1413 AN: 4820

European-Finnish (FIN) AF: 0.270 AC: 2847 AN: 10548

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.184 AC: 12493 AN: 67978

Other (OTH) AF: 0.227 AC: 481 AN: 2116

Alfa AF: 0.206 Hom.: 9354

Bravo AF: 0.247

Asia WGS AF: 0.399 AC: 1382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.6
DANN	Benign	0.62
PhyloP100		0.87
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: rs453503; hg19: chr6-89900599;