rs1186903

Positions:

• chr6-89217852-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001267582.2(GABRR1):​c.-242+3423C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,946 control chromosomes in the GnomAD database, including 10,798 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 0.37 (10746 hom., cov: 31)
  • Exomes 𝑓: 0.31 (52 hom.)
• Consequence: GABRR1 NM_001267582.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRR1	NM_001267582.2	c.-242+3423C>T		intron_variant			NP_001254511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000369451.7	c.-239+3423C>T		intron_variant		5		ENSP00000358463

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55561 AN: 151744 Hom.: 10739 Cov.: 31

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.0946

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.335

GnomAD4 exome AF: 0.312 AC: 338 AN: 1084 Hom.: 52 AF XY: 0.300 AC XY: 181 AN XY: 604

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.0625

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.563

Gnomad4 NFE exome AF: 0.348

Gnomad4 OTH exome AF: 0.239

GnomAD4 genome AF: 0.366 AC: 55592 AN: 151862 Hom.: 10746 Cov.: 31 AF XY: 0.360 AC XY: 26744 AN XY: 74200

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.0944

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.333

Alfa AF: 0.368 Hom.: 4651

Bravo AF: 0.358

Asia WGS AF: 0.265 AC: 923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1186903; hg19: chr6-89927571;