rs7020345

Variant names:

• chr9-98406295-A-G
• rs7020345
• NM_005458.8:c.1237-154T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-98406295-A-G
• chr9-98406295-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005458.8(GABBR2):​c.1237-154T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,298 control chromosomes in the GnomAD database, including 3,651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.21 (3651 hom., cov: 33)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.32
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 9-98406295-A-G is Benign according to our data. Variant chr9-98406295-A-G is described in ClinVar as Benign. ClinVar VariationId is 1267765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.1237-154T>C		intron_variant	Intron 7 of 18	ENST00000259455.4	NP_005449.5
GABBR2	XM_017015331.3	c.943-154T>C		intron_variant	Intron 6 of 17		XP_016870820.1
GABBR2	XM_005252316.6	c.463-154T>C		intron_variant	Intron 5 of 16		XP_005252373.1
GABBR2	XM_017015332.3	c.463-154T>C		intron_variant	Intron 4 of 15		XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.1237-154T>C		intron_variant	Intron 7 of 18	1	NM_005458.8	ENSP00000259455.2
GABBR2	ENST00000637410.1	n.1015-154T>C		intron_variant	Intron 7 of 18	5

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32663 AN: 152180 Hom.: 3647 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.215 AC: 32689 AN: 152298 Hom.: 3651 Cov.: 33 AF XY: 0.214 AC XY: 15973 AN XY: 74478

African (AFR) AF: 0.166 AC: 6902 AN: 41562

American (AMR) AF: 0.200 AC: 3057 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 880 AN: 3472

East Asian (EAS) AF: 0.186 AC: 963 AN: 5184

South Asian (SAS) AF: 0.168 AC: 810 AN: 4832

European-Finnish (FIN) AF: 0.246 AC: 2609 AN: 10602

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16806 AN: 68014

Other (OTH) AF: 0.223 AC: 472 AN: 2114

Alfa AF: 0.237 Hom.: 7140

Bravo AF: 0.210

Asia WGS AF: 0.171 AC: 596 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.73
PhyloP100		1.3
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: rs7020345; hg19: chr9-101168577;