rs13295101

Variant names:

• chr9-98507948-T-C
• rs13295101
• NM_005458.8:c.631-11434A>G

Variant summary

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

The NM_005458.8(GABBR2):​c.631-11434A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,992 control chromosomes in the GnomAD database, including 9,327 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 0.35 (9327 hom., cov: 32)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810
• Publications: 5 publications found

Genes affected

GABBR2 (HGNC:4507): (gamma-aminobutyric acid type B receptor subunit 2) The multi-pass membrane protein encoded by this gene belongs to the G-protein coupled receptor 3 family and GABA-B receptor subfamily. The GABA-B receptors inhibit neuronal activity through G protein-coupled second-messenger systems, which regulate the release of neurotransmitters, and the activity of ion channels and adenylyl cyclase. This receptor subunit forms an active heterodimeric complex with GABA-B receptor subunit 1, neither of which is effective on its own. Allelic variants of this gene have been associated with nicotine dependence.[provided by RefSeq, Jan 2010]

GABBR2 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 59

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder with poor language and loss of hand skills

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• atypical Rett syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.631-11434A>G		intron_variant	Intron 3 of 18	ENST00000259455.4	NP_005449.5
GABBR2	XM_017015331.3	c.337-11434A>G		intron_variant	Intron 2 of 17		XP_016870820.1
GABBR2	XM_005252316.6	c.-144-11434A>G		intron_variant	Intron 1 of 16		XP_005252373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.631-11434A>G		intron_variant	Intron 3 of 18	1	NM_005458.8	ENSP00000259455.2

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52466 AN: 151874 Hom.: 9327 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.345 AC: 52483 AN: 151992 Hom.: 9327 Cov.: 32 AF XY: 0.339 AC XY: 25156 AN XY: 74302

African (AFR) AF: 0.342 AC: 14168 AN: 41448

American (AMR) AF: 0.263 AC: 4010 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1392 AN: 3468

East Asian (EAS) AF: 0.183 AC: 947 AN: 5168

South Asian (SAS) AF: 0.382 AC: 1838 AN: 4814

European-Finnish (FIN) AF: 0.324 AC: 3426 AN: 10564

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25518 AN: 67948

Other (OTH) AF: 0.347 AC: 732 AN: 2108

Alfa AF: 0.368 Hom.: 32087

Bravo AF: 0.339

Asia WGS AF: 0.278 AC: 964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.52
PhyloP100		-0.81
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: rs13295101; hg19: chr9-101270230;