rs453503

Positions:

• chr6-89190880-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.573-633G>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

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=-0.8).
• 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/exons	MANE	UniProt
GABRR1	NM_002042.5	c.573-633G>A		intron_variant		ENST00000454853.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRR1	ENST00000454853.7	c.573-633G>A		intron_variant		1	NM_002042.5	P1
GABRR1	ENST00000369451.7	c.312-633G>A		intron_variant		5
GABRR1	ENST00000435811.5	c.522-633G>A		intron_variant		2
GABRR1	ENST00000457434.1	c.*534-633G>A		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.227

Alfa AF: 0.197 Hom.: 2825

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

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: rs453503; hg19: chr6-89900599;