ENST00000355973.7:c.*2+12023G>A

Variant names:

• chr6-29591518-C-T
• rs1233384
• ENST00000355973.7:c.*2+12023G>A

Variant summary

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

The ENST00000355973.7(GABBR1):​c.*2+12023G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,190 control chromosomes in the GnomAD database, including 1,479 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 0.14 (1479 hom., cov: 32)
• Consequence: GABBR1 ENST00000355973.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527
• Publications: 23 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR1	ENST00000355973.7	c.*2+12023G>A		intron_variant	Intron 18 of 18	2		ENSP00000348248.3

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20647 AN: 152072 Hom.: 1476 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.136 AC: 20662 AN: 152190 Hom.: 1479 Cov.: 32 AF XY: 0.136 AC XY: 10152 AN XY: 74394

African (AFR) AF: 0.115 AC: 4764 AN: 41520

American (AMR) AF: 0.181 AC: 2774 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3472

East Asian (EAS) AF: 0.216 AC: 1116 AN: 5176

South Asian (SAS) AF: 0.102 AC: 490 AN: 4818

European-Finnish (FIN) AF: 0.155 AC: 1647 AN: 10596

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8958 AN: 68004

Other (OTH) AF: 0.128 AC: 270 AN: 2112

Alfa AF: 0.140 Hom.: 6205

Bravo AF: 0.140

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.53
PhyloP100		-0.53
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: rs1233384; hg19: chr6-29559295;