6-29624654-T-C

Variant names:

• chr6-29624654-T-C
• rs2267635
• NM_001470.4:c.658-630A>G

Variant summary

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

The NM_001470.4(GABBR1):​c.658-630A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 151,660 control chromosomes in the GnomAD database, including 276 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 0.053 (276 hom., cov: 31)
• Consequence: GABBR1 NM_001470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39
• Publications: 17 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001470.4. 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
	GABBR1	NM_001470.4	MANE Select	c.658-630A>G		intron	N/A	NP_001461.1	A0A1U9X7R0
	GABBR1	NM_021904.4		c.472-630A>G		intron	N/A	NP_068704.2	Q9UBS5-3
	GABBR1	NM_021903.3		c.307-630A>G		intron	N/A	NP_068703.1	Q5SUJ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR1	ENST00000377034.9	TSL:1 MANE Select	c.658-630A>G		intron	N/A	ENSP00000366233.4	Q9UBS5-1
	GABBR1	ENST00000377012.9	TSL:1	c.307-630A>G		intron	N/A	ENSP00000366211.4	Q9UBS5-2
	GABBR1	ENST00000476670.3	TSL:4	c.673-630A>G		intron	N/A	ENSP00000417332.2	C9J342

Frequencies

GnomAD3 genomes AF: 0.0528 AC: 8006 AN: 151542 Hom.: 278 Cov.: 31

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0550

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0986

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0285

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0596

Gnomad OTH AF: 0.0644

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

GnomAD4 genome AF: 0.0528 AC: 8003 AN: 151660 Hom.: 276 Cov.: 31 AF XY: 0.0533 AC XY: 3950 AN XY: 74094

African (AFR) AF: 0.0272 AC: 1122 AN: 41276

American (AMR) AF: 0.0550 AC: 838 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3462

East Asian (EAS) AF: 0.0984 AC: 508 AN: 5160

South Asian (SAS) AF: 0.136 AC: 649 AN: 4784

European-Finnish (FIN) AF: 0.0285 AC: 300 AN: 10520

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 292

European-Non Finnish (NFE) AF: 0.0596 AC: 4047 AN: 67908

Other (OTH) AF: 0.0651 AC: 137 AN: 2104

Alfa AF: 0.0558 Hom.: 637

Bravo AF: 0.0528

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.015
DANN	Benign	0.57
PhyloP100		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2267635; hg19: chr6-29592431;