rs407206

Positions:

• chr6-89185249-G-A

Variant summary

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

The NM_002042.5(GABRR1):​c.796+61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,599,704 control chromosomes in the GnomAD database, including 76,982 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 0.25 (5425 hom., cov: 30)
  • Exomes 𝑓: 0.31 (71557 hom.)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560

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 (NFE) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRR1	NM_002042.5	c.796+61C>T		intron_variant		ENST00000454853.7	NP_002033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000454853.7	c.796+61C>T		intron_variant		1	NM_002042.5	ENSP00000412673	P1
GABRR1	ENST00000369451.7	c.535+61C>T		intron_variant		5		ENSP00000358463
GABRR1	ENST00000435811.5	c.745+61C>T		intron_variant		2		ENSP00000394687
GABRR1	ENST00000457434.1	c.*757+61C>T		intron_variant, NMD_transcript_variant		5		ENSP00000410130

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37946 AN: 151710 Hom.: 5428 Cov.: 30

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.308 AC: 446092 AN: 1447876 Hom.: 71557 AF XY: 0.308 AC XY: 222041 AN XY: 721088

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.341

Gnomad4 EAS exome AF: 0.149

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.321

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.285

GnomAD4 genome AF: 0.250 AC: 37948 AN: 151828 Hom.: 5425 Cov.: 30 AF XY: 0.248 AC XY: 18411 AN XY: 74180

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.270

Alfa AF: 0.315 Hom.: 10404

Bravo AF: 0.236

Asia WGS AF: 0.164 AC: 571 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	1.9
DANN	Benign	0.31

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: rs407206; hg19: chr6-89894968; COSMIC: COSV65619032;