9-98370159-T-C

Variant names:

• chr9-98370159-T-C
• rs585819
• NM_005458.8:c.1770+1305A>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.1770+1305A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,910 control chromosomes in the GnomAD database, including 12,219 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 0.36 (12219 hom., cov: 31)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.53
• Publications: 3 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005458.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR2	NM_005458.8	MANE Select	c.1770+1305A>G		intron	N/A	NP_005449.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR2	ENST00000259455.4	TSL:1 MANE Select	c.1770+1305A>G		intron	N/A	ENSP00000259455.2
	GABBR2	ENST00000634457.1	TSL:5	c.108+1305A>G		intron	N/A	ENSP00000489352.1
	GABBR2	ENST00000634314.1	TSL:3	n.275+1305A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55017 AN: 151790 Hom.: 12185 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.363 AC: 55096 AN: 151910 Hom.: 12219 Cov.: 31 AF XY: 0.362 AC XY: 26852 AN XY: 74226

African (AFR) AF: 0.630 AC: 26072 AN: 41392

American (AMR) AF: 0.237 AC: 3616 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1290 AN: 3464

East Asian (EAS) AF: 0.176 AC: 908 AN: 5162

South Asian (SAS) AF: 0.354 AC: 1705 AN: 4812

European-Finnish (FIN) AF: 0.274 AC: 2898 AN: 10558

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17543 AN: 67926

Other (OTH) AF: 0.353 AC: 745 AN: 2112

Alfa AF: 0.301 Hom.: 22948

Bravo AF: 0.369

Asia WGS AF: 0.311 AC: 1085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.36
PhyloP100		-2.5
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: rs585819; hg19: chr9-101132441;