rs29220

Positions:

• chr6-29621889-C-G

Variant summary

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

The NM_001470.4(GABBR1):​c.1066-72G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,483,088 control chromosomes in the GnomAD database, including 60,706 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 0.31 (7667 hom., cov: 32)
  • Exomes 𝑓: 0.28 (53039 hom.)
• Consequence: GABBR1 NM_001470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR1	NM_001470.4	c.1066-72G>C		intron_variant		ENST00000377034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR1	ENST00000377034.9	c.1066-72G>C		intron_variant		1	NM_001470.4	P1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47338 AN: 151980 Hom.: 7650 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.316

GnomAD4 exome AF: 0.276 AC: 367437 AN: 1330990 Hom.: 53039 Cov.: 19 AF XY: 0.278 AC XY: 185804 AN XY: 668912

Gnomad4 AFR exome AF: 0.346

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.195

Gnomad4 EAS exome AF: 0.389

Gnomad4 SAS exome AF: 0.382

Gnomad4 FIN exome AF: 0.418

Gnomad4 NFE exome AF: 0.255

Gnomad4 OTH exome AF: 0.279

GnomAD4 genome AF: 0.312 AC: 47391 AN: 152098 Hom.: 7667 Cov.: 32 AF XY: 0.320 AC XY: 23820 AN XY: 74324

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.321

Alfa AF: 0.267 Hom.: 3146

Bravo AF: 0.302

Asia WGS AF: 0.460 AC: 1600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.63
DANN	Benign	0.63

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: rs29220; hg19: chr6-29589666;