rs7044793

Positions:

• chr9-98519257-C-A
• chr9-98519257-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005458.8(GABBR2):​c.630+22616G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,030 control chromosomes in the GnomAD database, including 9,434 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 0.35 (9434 hom., cov: 32)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.630+22616G>T		intron_variant		ENST00000259455.4	NP_005449.5
GABBR2	XM_005252316.6	c.-145+19289G>T		intron_variant			XP_005252373.1
GABBR2	XM_017015331.3	c.336+22616G>T		intron_variant			XP_016870820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.630+22616G>T		intron_variant		1	NM_005458.8	ENSP00000259455	P1
GABBR2	ENST00000477471.1	n.417+22616G>T		intron_variant, non_coding_transcript_variant		3
GABBR2	ENST00000634227.1	n.404+22616G>T		intron_variant, non_coding_transcript_variant		5
GABBR2	ENST00000637410.1	n.408+22616G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52773 AN: 151912 Hom.: 9434 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.347 AC: 52790 AN: 152030 Hom.: 9434 Cov.: 32 AF XY: 0.341 AC XY: 25301 AN XY: 74290

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.346

Alfa AF: 0.217 Hom.: 513

Bravo AF: 0.340

Asia WGS AF: 0.282 AC: 980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.8
DANN	Benign	0.73

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: rs7044793; hg19: chr9-101281539;