rs1003581

Variant names:

• chr6-29572427-G-A
• rs1003581
• ENST00000355973.7:c.*3-16077C>T

Variant summary

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

The ENST00000355973.7(GABBR1):​c.*3-16077C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,992 control chromosomes in the GnomAD database, including 4,083 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 0.22 (4083 hom., cov: 32)
• Consequence: GABBR1 ENST00000355973.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758
• Publications: 21 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.381 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR1	ENST00000355973.7	TSL:2	c.*3-16077C>T		intron	N/A	ENSP00000348248.3	Q9UBS5-2

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33804 AN: 151876 Hom.: 4084 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.222 AC: 33818 AN: 151992 Hom.: 4083 Cov.: 32 AF XY: 0.230 AC XY: 17054 AN XY: 74282

African (AFR) AF: 0.263 AC: 10909 AN: 41444

American (AMR) AF: 0.188 AC: 2872 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 802 AN: 3470

East Asian (EAS) AF: 0.368 AC: 1901 AN: 5168

South Asian (SAS) AF: 0.396 AC: 1910 AN: 4820

European-Finnish (FIN) AF: 0.272 AC: 2867 AN: 10540

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11843 AN: 67970

Other (OTH) AF: 0.243 AC: 513 AN: 2108

Alfa AF: 0.199 Hom.: 5200

Bravo AF: 0.217

Asia WGS AF: 0.315 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.46
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1003581;

hg19: chr6-29540204;