ENST00000355973.7:c.*3-15638C>T

Variant names:

• chr6-29571988-G-A
• rs3025652
• ENST00000355973.7:c.*3-15638C>T

Variant summary

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

The ENST00000355973.7(GABBR1):​c.*3-15638C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 150,460 control chromosomes in the GnomAD database, including 2,882 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 0.19 (2882 hom., cov: 31)
• Consequence: GABBR1 ENST00000355973.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809
• Publications: 9 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 = 0.239 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR1	ENST00000355973.7	TSL:2	c.*3-15638C>T		intron	N/A	ENSP00000348248.3

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29121 AN: 150342 Hom.: 2882 Cov.: 31

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.194 AC: 29123 AN: 150460 Hom.: 2882 Cov.: 31 AF XY: 0.198 AC XY: 14506 AN XY: 73432

African (AFR) AF: 0.217 AC: 8888 AN: 40966

American (AMR) AF: 0.168 AC: 2540 AN: 15108

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3460

East Asian (EAS) AF: 0.222 AC: 1138 AN: 5128

South Asian (SAS) AF: 0.251 AC: 1197 AN: 4766

European-Finnish (FIN) AF: 0.279 AC: 2866 AN: 10282

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.166 AC: 11210 AN: 67480

Other (OTH) AF: 0.209 AC: 435 AN: 2078

Alfa AF: 0.173 Hom.: 5339

Bravo AF: 0.186

Asia WGS AF: 0.218 AC: 757 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	0.11
DANN	Benign	0.56
PhyloP100		-0.81
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: rs3025652; hg19: chr6-29539765;