9-98335166-A-G

Variant names:

• chr9-98335166-A-G
• rs6478676
• NM_005458.8:c.1894-23961T>C

Variant summary

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

The NM_005458.8(GABBR2):​c.1894-23961T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,906 control chromosomes in the GnomAD database, including 24,461 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 0.56 (24461 hom., cov: 31)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388
• Publications: 2 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)
• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR2	NM_005458.8	MANE Select	c.1894-23961T>C		intron	N/A	NP_005449.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR2	ENST00000259455.4	TSL:1 MANE Select	c.1894-23961T>C		intron	N/A	ENSP00000259455.2	O75899
	GABBR2	ENST00000931526.1		c.1828-23961T>C		intron	N/A	ENSP00000601585.1
	GABBR2	ENST00000947376.1		c.1813-23961T>C		intron	N/A	ENSP00000617435.1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85224 AN: 151788 Hom.: 24448 Cov.: 31

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.561 AC: 85274 AN: 151906 Hom.: 24461 Cov.: 31 AF XY: 0.558 AC XY: 41460 AN XY: 74246

African (AFR) AF: 0.670 AC: 27740 AN: 41394

American (AMR) AF: 0.464 AC: 7084 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2002 AN: 3472

East Asian (EAS) AF: 0.457 AC: 2357 AN: 5162

South Asian (SAS) AF: 0.537 AC: 2580 AN: 4802

European-Finnish (FIN) AF: 0.507 AC: 5348 AN: 10538

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36225 AN: 67962

Other (OTH) AF: 0.563 AC: 1188 AN: 2112

Alfa AF: 0.525 Hom.: 11494

Bravo AF: 0.561

Asia WGS AF: 0.474 AC: 1651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.7
DANN	Benign	0.66
PhyloP100		0.39
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: rs6478676; hg19: chr9-101097448;