rs914478

chr6-89221200-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+75A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,098 control chromosomes in the GnomAD database, including 10,262 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 0.36 (10241 hom., cov: 31)
  • Exomes 𝑓: 0.39 (21 hom.)
• Consequence: GABRR1 NM_001267582.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRR1	NM_001267582.2	c.-242+75A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRR1	ENST00000369451.7	c.-239+75A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54230 AN: 151682 Hom.: 10234 Cov.: 31

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0947

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.389 AC: 116 AN: 298 Hom.: 21 AF XY: 0.400 AC XY: 72 AN XY: 180

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.418

Gnomad4 NFE exome AF: 0.396

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.357 AC: 54264 AN: 151800 Hom.: 10241 Cov.: 31 AF XY: 0.352 AC XY: 26130 AN XY: 74178

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.0945

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.328

Alfa AF: 0.372 Hom.: 1321

Bravo AF: 0.350

Asia WGS AF: 0.262 AC: 911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.8
Dann	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs914478; hg19: chr6-89930919;