rs368873

chr6-89183443-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.797-1386C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,980 control chromosomes in the GnomAD database, including 33,646 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 0.66 (33646 hom., cov: 31)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

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 (NFE) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRR1	NM_002042.5	c.797-1386C>T		intron_variant		ENST00000454853.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRR1	ENST00000454853.7	c.797-1386C>T		intron_variant		1	NM_002042.5	P1
GABRR1	ENST00000369451.7	c.536-1386C>T		intron_variant		5
GABRR1	ENST00000435811.5	c.746-1386C>T		intron_variant		2
GABRR1	ENST00000457434.1	c.*758-1386C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100435 AN: 151862 Hom.: 33606 Cov.: 31

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.662 AC: 100541 AN: 151980 Hom.: 33646 Cov.: 31 AF XY: 0.652 AC XY: 48415 AN XY: 74270

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.743

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.697

Alfa AF: 0.704 Hom.: 21701

Bravo AF: 0.661

Asia WGS AF: 0.560 AC: 1947 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	3.4
Dann	Benign	0.34

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: rs368873; hg19: chr6-89893162;