NM_005458.8:c.1771-3797G>A

Variant names:

• chr9-98366634-C-T
• rs3780428
• NM_005458.8:c.1771-3797G>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.1771-3797G>A 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 152,058 control chromosomes in the GnomAD database, including 11,986 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 (11986 hom., cov: 32)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800
• Publications: 11 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.1771-3797G>A		intron_variant	Intron 12 of 18	ENST00000259455.4	NP_005449.5
GABBR2	XM_017015331.3	c.1477-3797G>A		intron_variant	Intron 11 of 17		XP_016870820.1
GABBR2	XM_005252316.6	c.997-3797G>A		intron_variant	Intron 10 of 16		XP_005252373.1
GABBR2	XM_017015332.3	c.997-3797G>A		intron_variant	Intron 9 of 15		XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.1771-3797G>A		intron_variant	Intron 12 of 18	1	NM_005458.8	ENSP00000259455.2

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55103 AN: 151940 Hom.: 11963 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.363 AC: 55172 AN: 152058 Hom.: 11986 Cov.: 32 AF XY: 0.355 AC XY: 26366 AN XY: 74328

African (AFR) AF: 0.614 AC: 25447 AN: 41466

American (AMR) AF: 0.259 AC: 3963 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 856 AN: 3470

East Asian (EAS) AF: 0.170 AC: 879 AN: 5172

South Asian (SAS) AF: 0.175 AC: 841 AN: 4802

European-Finnish (FIN) AF: 0.256 AC: 2708 AN: 10578

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.286 AC: 19446 AN: 67974

Other (OTH) AF: 0.366 AC: 772 AN: 2108

Alfa AF: 0.312 Hom.: 25978

Bravo AF: 0.377

Asia WGS AF: 0.232 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.86
DANN	Benign	0.74
PhyloP100		-0.80
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: rs3780428; hg19: chr9-101128916;