6-29624654-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR1	NM_001470.4	c.658-630A>G		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.658-630A>G		intron_variant	Intron 6 of 22	1	NM_001470.4	ENSP00000366233.4

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

Gnomad4 AFR AF: 0.0272

Gnomad4 AMR AF: 0.0550

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0984

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0285

Gnomad4 NFE AF: 0.0596

Gnomad4 OTH AF: 0.0651

Alfa AF: 0.0536 Hom.: 157

Bravo AF: 0.0528

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.015
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs2267635; hg19: chr6-29592431;