rs1003581

Variant names:

• chr6-29572427-G-A
• rs1003581
• ENST00000355973.7:c.*3-16077C>T

Variant summary

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

The ENST00000355973.7(GABBR1):​c.*3-16077C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,992 control chromosomes in the GnomAD database, including 4,083 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 0.22 (4083 hom., cov: 32)
• Consequence: GABBR1 ENST00000355973.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR1	ENST00000355973.7	c.*3-16077C>T		intron_variant	Intron 18 of 18	2		ENSP00000348248.3

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33804 AN: 151876 Hom.: 4084 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.222 AC: 33818 AN: 151992 Hom.: 4083 Cov.: 32 AF XY: 0.230 AC XY: 17054 AN XY: 74282

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.243

Alfa AF: 0.190 Hom.: 2130

Bravo AF: 0.217

Asia WGS AF: 0.315 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1003581; hg19: chr6-29540204;