rs17184416

Variant names:

• chr6-29625701-A-G
• rs17184416
• NM_001470.4:c.658-1677T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.75).
• 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 rank	MANE	Protein	UniProt
GABBR1	NM_001470.4	c.658-1677T>C		intron_variant	Intron 6 of 22	ENST00000377034.9	NP_001461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR1	ENST00000377034.9	c.658-1677T>C		intron_variant	Intron 6 of 22	1	NM_001470.4	ENSP00000366233.4

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

African (AFR) AF: 0.0894 AC: 3706 AN: 41470

American (AMR) AF: 0.0998 AC: 1526 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0862 AC: 299 AN: 3468

East Asian (EAS) AF: 0.127 AC: 656 AN: 5172

South Asian (SAS) AF: 0.158 AC: 760 AN: 4806

European-Finnish (FIN) AF: 0.0439 AC: 465 AN: 10598

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7033 AN: 67972

Other (OTH) AF: 0.119 AC: 251 AN: 2114

Alfa AF: 0.0932 Hom.: 80

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
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17184416; hg19: chr6-29593478;