rs3205936

Variant names:

• chr9-98385715-G-A
• rs3205936
• NM_005458.8:c.1587C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-98385715-G-A
• chr9-98385715-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005458.8(GABBR2):​c.1587C>T​(p.Leu529Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00914 in 1,605,760 control chromosomes in the GnomAD database, including 1,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (651 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (537 hom.)
• Consequence: GABBR2 NM_005458.8 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.363
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• neurodevelopmental disorder with poor language and loss of hand skills

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• atypical Rett syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 9-98385715-G-A is Benign according to our data. Variant chr9-98385715-G-A is described in ClinVar as Benign. ClinVar VariationId is 462125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.363 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005458.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR2	NM_005458.8	MANE Select	c.1587C>T	p.Leu529Leu	synonymous	Exon 11 of 19	NP_005449.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR2	ENST00000259455.4	TSL:1 MANE Select	c.1587C>T	p.Leu529Leu	synonymous	Exon 11 of 19	ENSP00000259455.2	O75899
	GABBR2	ENST00000931526.1		c.1521C>T	p.Leu507Leu	synonymous	Exon 10 of 18	ENSP00000601585.1
	GABBR2	ENST00000947376.1		c.1506C>T	p.Leu502Leu	synonymous	Exon 10 of 18	ENSP00000617435.1

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7526 AN: 152130 Hom.: 652 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0213

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.0354

GnomAD2 exomes AF: 0.0124 AC: 3126 AN: 251432 AF XY: 0.00908

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.00758

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000484

Gnomad OTH exome AF: 0.00668

GnomAD4 exome AF: 0.00491 AC: 7142 AN: 1453512 Hom.: 537 Cov.: 27 AF XY: 0.00414 AC XY: 2998 AN XY: 723668

African (AFR) AF: 0.174 AC: 5780 AN: 33272

American (AMR) AF: 0.00890 AC: 398 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39666

South Asian (SAS) AF: 0.000360 AC: 31 AN: 86092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00591 AC: 34 AN: 5752

European-Non Finnish (NFE) AF: 0.000188 AC: 208 AN: 1104368

Other (OTH) AF: 0.0115 AC: 690 AN: 60140

GnomAD4 genome AF: 0.0495 AC: 7529 AN: 152248 Hom.: 651 Cov.: 32 AF XY: 0.0472 AC XY: 3511 AN XY: 74438

African (AFR) AF: 0.171 AC: 7085 AN: 41514

American (AMR) AF: 0.0213 AC: 325 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000515 AC: 35 AN: 68024

Other (OTH) AF: 0.0350 AC: 74 AN: 2112

Alfa AF: 0.0430 Hom.: 433

Bravo AF: 0.0577

Asia WGS AF: 0.00953 AC: 34 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000652

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Epileptic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.3
DANN	Benign	0.67
PhyloP100		-0.36
Mutation Taster		=99/1	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: rs3205936; hg19: chr9-101147997;