6-89205787-C-T

Position:

• chr6-89205787-C-T

Variant summary

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

The NM_002042.5(GABRR1):​c.123-2302G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 152,068 control chromosomes in the GnomAD database, including 53,396 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 0.84 (53391 hom., cov: 30)
  • Exomes 𝑓: 0.86 (5 hom.)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRR1	NM_002042.5	c.123-2302G>A		intron_variant		ENST00000454853.7	NP_002033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000454853.7	c.123-2302G>A		intron_variant		1	NM_002042.5	ENSP00000412673	P1

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127019 AN: 151934 Hom.: 53345 Cov.: 30

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.831

GnomAD4 exome AF: 0.857 AC: 12 AN: 14 Hom.: 5 Cov.: 0 AF XY: 0.833 AC XY: 10 AN XY: 12

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.833

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.836 AC: 127123 AN: 152054 Hom.: 53391 Cov.: 30 AF XY: 0.838 AC XY: 62325 AN XY: 74336

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.871

Gnomad4 ASJ AF: 0.879

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.901

Gnomad4 NFE AF: 0.856

Gnomad4 OTH AF: 0.833

Alfa AF: 0.852 Hom.: 17370

Bravo AF: 0.833

Asia WGS AF: 0.826 AC: 2873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.70
DANN	Benign	0.47

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: rs2297389; hg19: chr6-89915506;