rs1233399

Positions:

• chr6-29571705-G-A

Variant summary

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

The ENST00000355973.7(GABBR1):​c.*3-15355C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,132 control chromosomes in the GnomAD database, including 2,600 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 0.18 (2600 hom., cov: 32)
• Consequence: GABBR1 ENST00000355973.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR1	ENST00000355973.7	c.*3-15355C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28067 AN: 152014 Hom.: 2598 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.185 AC: 28080 AN: 152132 Hom.: 2600 Cov.: 32 AF XY: 0.183 AC XY: 13635 AN XY: 74364

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.182

Alfa AF: 0.197 Hom.: 3637

Bravo AF: 0.192

Asia WGS AF: 0.150 AC: 519 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.19

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1233399; hg19: chr6-29539482;