9-98380522-C-T

Variant names:

• chr9-98380522-C-T
• rs3780422
• NM_005458.8:c.1662+5118G>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.1662+5118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,160 control chromosomes in the GnomAD database, including 11,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: 𝑓 0.37 (11840 hom., cov: 34)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.1662+5118G>A		intron_variant	Intron 11 of 18	ENST00000259455.4	NP_005449.5
GABBR2	XM_017015331.3	c.1368+5118G>A		intron_variant	Intron 10 of 17		XP_016870820.1
GABBR2	XM_005252316.6	c.888+5118G>A		intron_variant	Intron 9 of 16		XP_005252373.1
GABBR2	XM_017015332.3	c.888+5118G>A		intron_variant	Intron 8 of 15		XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.1662+5118G>A		intron_variant	Intron 11 of 18	1	NM_005458.8	ENSP00000259455.2
GABBR2	ENST00000634314.1	n.167+5118G>A		intron_variant	Intron 2 of 3	3
GABBR2	ENST00000637410.1	n.1440+5118G>A		intron_variant	Intron 11 of 18	5

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56882 AN: 152042 Hom.: 11834 Cov.: 34

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.374 AC: 56885 AN: 152160 Hom.: 11840 Cov.: 34 AF XY: 0.376 AC XY: 27942 AN XY: 74368

African (AFR) AF: 0.195 AC: 8111 AN: 41532

American (AMR) AF: 0.327 AC: 4998 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1497 AN: 3470

East Asian (EAS) AF: 0.523 AC: 2708 AN: 5176

South Asian (SAS) AF: 0.439 AC: 2117 AN: 4820

European-Finnish (FIN) AF: 0.470 AC: 4967 AN: 10564

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

European-Non Finnish (NFE) AF: 0.459 AC: 31173 AN: 67986

Other (OTH) AF: 0.384 AC: 811 AN: 2114

Alfa AF: 0.406 Hom.: 4963

Bravo AF: 0.355

Asia WGS AF: 0.387 AC: 1346 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	5.9
DANN	Benign	0.48
PhyloP100		0.15
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: rs3780422; hg19: chr9-101142804;