chr9-98311161-C-T

Position:

• chr9-98311161-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_005458.8(GABBR2):​c.1938G>A​(p.Glu646Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000674 in 1,613,920 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00070 (10 hom.)
• Consequence: GABBR2 NM_005458.8 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.21

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 9-98311161-C-T is Benign according to our data. Variant chr9-98311161-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 531172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.21 with no splicing effect.
• BS2: High AC in GnomAd4 at 64 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.1938G>A	p.Glu646Glu	synonymous_variant	14/19	ENST00000259455.4	NP_005449.5
GABBR2	XM_017015331.3	c.1644G>A	p.Glu548Glu	synonymous_variant	13/18		XP_016870820.1
GABBR2	XM_005252316.6	c.1164G>A	p.Glu388Glu	synonymous_variant	12/17		XP_005252373.1
GABBR2	XM_017015332.3	c.1164G>A	p.Glu388Glu	synonymous_variant	11/16		XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.1938G>A	p.Glu646Glu	synonymous_variant	14/19	1	NM_005458.8	ENSP00000259455.2
GABBR2	ENST00000634457.1	c.232-4816G>A		intron_variant		5		ENSP00000489352.1
GABBR2	ENST00000635462.1	n.433G>A		non_coding_transcript_exon_variant	4/5	2
GABBR2	ENST00000637410.1	n.1716G>A		non_coding_transcript_exon_variant	14/19	5

Frequencies

GnomAD3 genomes AF: 0.000414 AC: 63 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00119 AC: 298 AN: 251408 Hom.: 4 AF XY: 0.00152 AC XY: 207 AN XY: 135866

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000492

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00679

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000449

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.000700 AC: 1023 AN: 1461626 Hom.: 10 Cov.: 29 AF XY: 0.000908 AC XY: 660 AN XY: 727132

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.000626

Gnomad4 ASJ exome AF: 0.000957

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00620

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.000288

Gnomad4 OTH exome AF: 0.000977

GnomAD4 genome AF: 0.000420 AC: 64 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.000524 AC XY: 39 AN XY: 74470

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000550 Hom.: 0

Bravo AF: 0.000276

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.00115

EpiControl AF: 0.000830

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	GABBR2: BP4, BP7 -

Epileptic encephalopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.0
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs79484588; hg19: chr9-101073443;