rs11788000

Variant names:

• chr9-98611587-G-A
• rs11788000
• NM_005458.8:c.322-33515C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-98611587-G-A
• chr9-98611587-G-C
• chr9-98611587-G-T

Variant summary

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

The NM_005458.8(GABBR2):​c.322-33515C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,026 control chromosomes in the GnomAD database, including 31,743 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 0.64 (31743 hom., cov: 33)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.322-33515C>T		intron_variant	Intron 1 of 18	ENST00000259455.4	NP_005449.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.322-33515C>T		intron_variant	Intron 1 of 18	1	NM_005458.8	ENSP00000259455.2
GABBR2	ENST00000637717.1	c.-63-33515C>T		intron_variant	Intron 1 of 2	5		ENSP00000490789.1

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97130 AN: 151908 Hom.: 31729 Cov.: 33

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.639 AC: 97172 AN: 152026 Hom.: 31743 Cov.: 33 AF XY: 0.634 AC XY: 47097 AN XY: 74308

African (AFR) AF: 0.566 AC: 23456 AN: 41420

American (AMR) AF: 0.570 AC: 8713 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2750 AN: 3470

East Asian (EAS) AF: 0.340 AC: 1760 AN: 5178

South Asian (SAS) AF: 0.587 AC: 2830 AN: 4820

European-Finnish (FIN) AF: 0.675 AC: 7132 AN: 10570

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48172 AN: 67974

Other (OTH) AF: 0.661 AC: 1395 AN: 2110

Alfa AF: 0.587 Hom.: 1955

Bravo AF: 0.628

Asia WGS AF: 0.508 AC: 1765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.39
PhyloP100		1.8
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: rs11788000; hg19: chr9-101373869;