rs2267633

Positions:

• chr6-29603064-A-G

Variant summary

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

The NM_001470.4(GABBR1):​c.*479T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 457,274 control chromosomes in the GnomAD database, including 6,103 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 0.13 (1420 hom., cov: 32)
  • Exomes 𝑓: 0.16 (4683 hom.)
• Consequence: GABBR1 NM_001470.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR1	NM_001470.4	c.*479T>C		3_prime_UTR_variant	23/23	ENST00000377034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR1	ENST00000377034.9	c.*479T>C		3_prime_UTR_variant	23/23	1	NM_001470.4	P1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19061 AN: 152152 Hom.: 1420 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.0626

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.154

GnomAD3 exomes AF: 0.157 AC: 21658 AN: 137566 Hom.: 2080 AF XY: 0.166 AC XY: 12341 AN XY: 74552

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.244

Gnomad SAS exome AF: 0.271

Gnomad FIN exome AF: 0.0534

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.155

GnomAD4 exome AF: 0.156 AC: 47607 AN: 305004 Hom.: 4683 Cov.: 0 AF XY: 0.169 AC XY: 29338 AN XY: 173640

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.122

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.237

Gnomad4 SAS exome AF: 0.275

Gnomad4 FIN exome AF: 0.0611

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.125 AC: 19070 AN: 152270 Hom.: 1420 Cov.: 32 AF XY: 0.128 AC XY: 9544 AN XY: 74456

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.0626

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.154

Alfa AF: 0.132 Hom.: 2591

Bravo AF: 0.126

Asia WGS AF: 0.214 AC: 745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.70
DANN	Benign	0.56

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: rs2267633; hg19: chr6-29570841;