rs55941866

chr6-29603800-G-A

Variant summary

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

The NM_001470.4(GABBR1):c.2713-84C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 1,066,380 control chromosomes in the GnomAD database, including 968 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 0.036 (198 hom., cov: 31)
  • Exomes 𝑓: 0.030 (770 hom.)
• Consequence: GABBR1 NM_001470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490

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=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR1	NM_001470.4	c.2713-84C>T		intron_variant		ENST00000377034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR1	ENST00000377034.9	c.2713-84C>T		intron_variant		1	NM_001470.4	P1

Frequencies

GnomAD3 genomes AF: 0.0362 AC: 5499 AN: 152036 Hom.: 199 Cov.: 31

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0935

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0476

Gnomad SAS AF: 0.0966

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0281

Gnomad OTH AF: 0.0374

GnomAD4 exome AF: 0.0299 AC: 27347 AN: 914226 Hom.: 770 AF XY: 0.0320 AC XY: 14278 AN XY: 446460

Gnomad4 AFR exome AF: 0.0148

Gnomad4 AMR exome AF: 0.0979

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.0456

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.0234

Gnomad4 NFE exome AF: 0.0221

Gnomad4 OTH exome AF: 0.0411

GnomAD4 genome AF: 0.0362 AC: 5504 AN: 152154 Hom.: 198 Cov.: 31 AF XY: 0.0379 AC XY: 2817 AN XY: 74390

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.0934

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0477

Gnomad4 SAS AF: 0.0981

Gnomad4 FIN AF: 0.0191

Gnomad4 NFE AF: 0.0281

Gnomad4 OTH AF: 0.0370

Alfa AF: 0.0299 Hom.: 10

Bravo AF: 0.0399

Asia WGS AF: 0.0710 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	7.1
Dann	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs55941866; hg19: chr6-29571577;