rs17184416

Positions:

• chr6-29625701-A-G
• chr6-29625701-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001470.4(GABBR1):​c.658-1677T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0978 in 152,088 control chromosomes in the GnomAD database, including 852 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 0.098 (852 hom., cov: 31)
• Consequence: GABBR1 NM_001470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247

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=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR1	NM_001470.4	c.658-1677T>C		intron_variant		ENST00000377034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR1	ENST00000377034.9	c.658-1677T>C		intron_variant		1	NM_001470.4	P1

Frequencies

GnomAD3 genomes AF: 0.0978 AC: 14870 AN: 151970 Hom.: 849 Cov.: 31

Gnomad AFR AF: 0.0894

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.0978 AC: 14877 AN: 152088 Hom.: 852 Cov.: 31 AF XY: 0.0988 AC XY: 7350 AN XY: 74362

Gnomad4 AFR AF: 0.0894

Gnomad4 AMR AF: 0.0998

Gnomad4 ASJ AF: 0.0862

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0927 Hom.: 76

Bravo AF: 0.103

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.9
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs17184416; hg19: chr6-29593478;