9-98630473-C-T

Variant names:

• chr9-98630473-C-T
• rs1547272
• NM_005458.8:c.322-52401G>A

Variant summary

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

The NM_005458.8(GABBR2):​c.322-52401G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 152,056 control chromosomes in the GnomAD database, including 36,632 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 0.69 (36632 hom., cov: 31)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.322-52401G>A		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.322-52401G>A		intron_variant	Intron 1 of 18	1	NM_005458.8	ENSP00000259455.2
GABBR2	ENST00000637717.1	c.-63-52401G>A		intron_variant	Intron 1 of 2	5		ENSP00000490789.1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104391 AN: 151940 Hom.: 36627 Cov.: 31

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.687 AC: 104423 AN: 152056 Hom.: 36632 Cov.: 31 AF XY: 0.682 AC XY: 50690 AN XY: 74310

African (AFR) AF: 0.593 AC: 24596 AN: 41452

American (AMR) AF: 0.602 AC: 9198 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 2905 AN: 3472

East Asian (EAS) AF: 0.401 AC: 2070 AN: 5166

South Asian (SAS) AF: 0.641 AC: 3088 AN: 4816

European-Finnish (FIN) AF: 0.757 AC: 8002 AN: 10576

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52085 AN: 67988

Other (OTH) AF: 0.700 AC: 1477 AN: 2110

Alfa AF: 0.744 Hom.: 41759

Bravo AF: 0.669

Asia WGS AF: 0.562 AC: 1955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.56
PhyloP100		0.27
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: rs1547272; hg19: chr9-101392755;