6-29603768-A-G

Position:

• chr6-29603768-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.2713-52T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,329,444 control chromosomes in the GnomAD database, including 11,242 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 0.12 (1410 hom., cov: 31)
  • Exomes 𝑓: 0.12 (9832 hom.)
• Consequence: GABBR1 NM_001470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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=-0.95).
• 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	Protein	UniProt
GABBR1	NM_001470.4	c.2713-52T>C		intron_variant		ENST00000377034.9	NP_001461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR1	ENST00000377034.9	c.2713-52T>C		intron_variant		1	NM_001470.4	ENSP00000366233	P1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18956 AN: 151618 Hom.: 1410 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.0624

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.155

GnomAD3 exomes AF: 0.133 AC: 12794 AN: 96082 Hom.: 1049 AF XY: 0.138 AC XY: 7009 AN XY: 50928

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.229

Gnomad SAS exome AF: 0.272

Gnomad FIN exome AF: 0.0455

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.119 AC: 140486 AN: 1177708 Hom.: 9832 Cov.: 18 AF XY: 0.123 AC XY: 70014 AN XY: 571070

Gnomad4 AFR exome AF: 0.0958

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.164

Gnomad4 EAS exome AF: 0.217

Gnomad4 SAS exome AF: 0.265

Gnomad4 FIN exome AF: 0.0578

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.125 AC: 18965 AN: 151736 Hom.: 1410 Cov.: 31 AF XY: 0.128 AC XY: 9487 AN XY: 74180

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.0624

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.154

Alfa AF: 0.121 Hom.: 1200

Bravo AF: 0.126

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.61

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: rs2076483; hg19: chr6-29571545;