rs762098632

Variant names:

• chr9-98406144-AAAAAC-A
• NM_005458.8:c.1237-8_1237-4delGTTTT

Your query was ambiguous. Multiple possible variants found:

• chr9-98406144-AAAAAC-A
• chr9-98406144-AAAAAC-AAAAACAAAAC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005458.8(GABBR2):​c.1237-8_1237-4delGTTTT variant causes a splice region, intron change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000064 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GABBR2 NM_005458.8 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.56

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.1237-8_1237-4delGTTTT		splice_region_variant, intron_variant	Intron 7 of 18	ENST00000259455.4	NP_005449.5
GABBR2	XM_017015331.3	c.943-8_943-4delGTTTT		splice_region_variant, intron_variant	Intron 6 of 17		XP_016870820.1
GABBR2	XM_005252316.6	c.463-8_463-4delGTTTT		splice_region_variant, intron_variant	Intron 5 of 16		XP_005252373.1
GABBR2	XM_017015332.3	c.463-8_463-4delGTTTT		splice_region_variant, 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.1237-8_1237-4delGTTTT		splice_region_variant, intron_variant	Intron 7 of 18	1	NM_005458.8	ENSP00000259455.2
GABBR2	ENST00000637410.1	n.1015-8_1015-4delGTTTT		splice_region_variant, intron_variant	Intron 7 of 18	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000637 AC: 9 AN: 1412678 Hom.: 0 AF XY: 0.00000852 AC XY: 6 AN XY: 704044

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000402

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000249

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.00000369

Gnomad4 OTH exome AF: 0.0000171

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-101168426;