rs404943

chr6-89181863-T-Cchr6-89181863-T-G

Variant summary

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

The NM_002042.5(GABRR1):c.949+42A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,538,000 control chromosomes in the GnomAD database, including 75,328 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 0.31 (7591 hom., cov: 32)
  • Exomes 𝑓: 0.31 (67737 hom.)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.836

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRR1	NM_002042.5	c.949+42A>G		intron_variant		ENST00000454853.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRR1	ENST00000454853.7	c.949+42A>G		intron_variant		1	NM_002042.5	P1
GABRR1	ENST00000369451.7	c.688+42A>G		intron_variant		5
GABRR1	ENST00000435811.5	c.898+42A>G		intron_variant		2
GABRR1	ENST00000457434.1	c.*910+42A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46998 AN: 151944 Hom.: 7600 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.284

GnomAD3 exomes AF: 0.334 AC: 74557 AN: 222942 Hom.: 13474 AF XY: 0.330 AC XY: 39801 AN XY: 120702

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.370

Gnomad ASJ exome AF: 0.250

Gnomad EAS exome AF: 0.639

Gnomad SAS exome AF: 0.351

Gnomad FIN exome AF: 0.377

Gnomad NFE exome AF: 0.280

Gnomad OTH exome AF: 0.305

GnomAD4 exome AF: 0.305 AC: 423057 AN: 1385938 Hom.: 67737 Cov.: 24 AF XY: 0.305 AC XY: 209194 AN XY: 686476

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.365

Gnomad4 ASJ exome AF: 0.249

Gnomad4 EAS exome AF: 0.622

Gnomad4 SAS exome AF: 0.346

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.288

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.309 AC: 47000 AN: 152062 Hom.: 7591 Cov.: 32 AF XY: 0.319 AC XY: 23737 AN XY: 74322

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.280

Alfa AF: 0.284 Hom.: 1383

Bravo AF: 0.306

Asia WGS AF: 0.434 AC: 1510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.2
Dann	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs404943; hg19: chr6-89891582; COSMIC: COSV65619025;