rs1233384

Positions:

• chr6-29591518-C-T

Variant summary

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

The ENST00000355973.7(GABBR1):​c.*2+12023G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,190 control chromosomes in the GnomAD database, including 1,479 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 0.14 (1479 hom., cov: 32)
• Consequence: GABBR1 ENST00000355973.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527

Genes affected

GABBR1 (HGNC:4070): (gamma-aminobutyric acid type B receptor subunit 1) This gene encodes a receptor for gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. This receptor functions as a heterodimer with GABA(B) receptor 2. Defects in this gene may underlie brain disorders such as schizophrenia and epilepsy. Alternative splicing generates multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jan 2016]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.29591518C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR1	ENST00000355973.7	c.*2+12023G>A		intron_variant		2		ENSP00000348248.3

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20647 AN: 152072 Hom.: 1476 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.136 AC: 20662 AN: 152190 Hom.: 1479 Cov.: 32 AF XY: 0.136 AC XY: 10152 AN XY: 74394

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.128

Alfa AF: 0.138 Hom.: 2597

Bravo AF: 0.140

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1233384; hg19: chr6-29559295;