6-29591518-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• 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

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.128

Alfa AF: 0.138 Hom.: 2597

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1233384; hg19: chr6-29559295;