rs914479

Positions:

• chr6-89220489-T-C

Variant summary

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

The NM_001267582.2(GABRR1):​c.-242+786A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,046 control chromosomes in the GnomAD database, including 11,783 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 0.38 (11783 hom., cov: 32)
• Consequence: GABRR1 NM_001267582.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRR1	NM_001267582.2	c.-242+786A>G		intron_variant			NP_001254511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000369451.7	c.-239+786A>G		intron_variant		5		ENSP00000358463

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58162 AN: 151928 Hom.: 11769 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.383 AC: 58206 AN: 152046 Hom.: 11783 Cov.: 32 AF XY: 0.378 AC XY: 28093 AN XY: 74328

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.0946

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.350

Alfa AF: 0.372 Hom.: 18764

Bravo AF: 0.373

Asia WGS AF: 0.275 AC: 959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.6
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs914479; hg19: chr6-89930208;