6-89208084-C-G

Position:

• chr6-89208084-C-G

Variant summary

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

The NM_002042.5(GABRR1):​c.123-4599G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,162 control chromosomes in the GnomAD database, including 30,485 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 0.63 (30485 hom., cov: 33)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575

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]

GABRR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRR1	NM_002042.5	c.123-4599G>C		intron_variant		ENST00000454853.7	NP_002033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000454853.7	c.123-4599G>C		intron_variant		1	NM_002042.5	ENSP00000412673.2

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95365 AN: 152042 Hom.: 30464 Cov.: 33

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.758

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.627 AC: 95447 AN: 152162 Hom.: 30485 Cov.: 33 AF XY: 0.616 AC XY: 45820 AN XY: 74404

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.662

Alfa AF: 0.500 Hom.: 1275

Bravo AF: 0.637

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.79

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: rs881293; hg19: chr6-89917803;