NM_005458.8:c.*308_*309insC

Variant names:

• chr9-98290275-T-TG
• rs796154585
• NM_005458.8:c.*308_*309insC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005458.8(GABBR2):​c.*308_*309insC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 138,544 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 27)
  • Exomes 𝑓: 0.00055 (1 hom.)
• Consequence: GABBR2 NM_005458.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 158 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.*308_*309insC		3_prime_UTR_variant	Exon 19 of 19	ENST00000259455.4	NP_005449.5
GABBR2	XM_017015331.3	c.*308_*309insC		3_prime_UTR_variant	Exon 18 of 18		XP_016870820.1
GABBR2	XM_005252316.6	c.*308_*309insC		3_prime_UTR_variant	Exon 17 of 17		XP_005252373.1
GABBR2	XM_017015332.3	c.*308_*309insC		3_prime_UTR_variant	Exon 16 of 16		XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455	c.*308_*309insC		3_prime_UTR_variant	Exon 19 of 19	1	NM_005458.8	ENSP00000259455.2

Frequencies

GnomAD3 genomes AF: 0.00129 AC: 158 AN: 122136 Hom.: 1 Cov.: 27

Gnomad AFR AF: 0.00755

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000741

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000227

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000464

Gnomad OTH AF: 0.00280

GnomAD4 exome AF: 0.000549 AC: 9 AN: 16394 Hom.: 1 Cov.: 0 AF XY: 0.000592 AC XY: 5 AN XY: 8442

Gnomad4 AFR exome AF: 0.00518

Gnomad4 AMR exome AF: 0.00216

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000292

Gnomad4 OTH exome AF: 0.000919

GnomAD4 genome AF: 0.00129 AC: 158 AN: 122150 Hom.: 1 Cov.: 27 AF XY: 0.00136 AC XY: 81 AN XY: 59636

Gnomad4 AFR AF: 0.00759

Gnomad4 AMR AF: 0.0000740

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000464

Gnomad4 OTH AF: 0.00279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs796154585; hg19: chr9-101052557;