6-29571705-G-A

Variant names:

• chr6-29571705-G-A
• rs1233399
• ENST00000355973.7:c.*3-15355C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000355973.7(GABBR1):​c.*3-15355C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,132 control chromosomes in the GnomAD database, including 2,600 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 0.18 (2600 hom., cov: 32)
• Consequence: GABBR1 ENST00000355973.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 20 publications found

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]

GABBR1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with language delay and variable cognitive abnormalities

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000355973.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR1	ENST00000355973.7	TSL:2	c.*3-15355C>T		intron	N/A	ENSP00000348248.3

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28067 AN: 152014 Hom.: 2598 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.185 AC: 28080 AN: 152132 Hom.: 2600 Cov.: 32 AF XY: 0.183 AC XY: 13635 AN XY: 74364

African (AFR) AF: 0.156 AC: 6486 AN: 41508

American (AMR) AF: 0.233 AC: 3569 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 544 AN: 3472

East Asian (EAS) AF: 0.197 AC: 1020 AN: 5174

South Asian (SAS) AF: 0.123 AC: 596 AN: 4830

European-Finnish (FIN) AF: 0.186 AC: 1969 AN: 10574

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13252 AN: 67972

Other (OTH) AF: 0.182 AC: 385 AN: 2110

Alfa AF: 0.196 Hom.: 9887

Bravo AF: 0.192

Asia WGS AF: 0.150 AC: 519 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.19
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1233399; hg19: chr6-29539482;