6-29588982-C-T

Position:

• chr6-29588982-C-T

Variant summary

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

The NM_007160.4(OR2H2):​c.*99C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 649,122 control chromosomes in the GnomAD database, including 1,691 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 0.050 (249 hom., cov: 32)
  • Exomes 𝑓: 0.067 (1442 hom.)
• Consequence: OR2H2 NM_007160.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17

Genes affected

OR2H2 (HGNC:8253): (olfactory receptor family 2 subfamily H member 2) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

GABBR1 (HGNC:4070): (gamma-aminobutyric acid type B receptor subunit 1) This gene encodes a receptor for gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. This receptor functions as a heterodimer with GABA(B) receptor 2. Defects in this gene may underlie brain disorders such as schizophrenia and epilepsy. Alternative splicing generates multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2H2	NM_007160.4	c.*99C>T		3_prime_UTR_variant	2/2	ENST00000641840.1	NP_009091.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2H2	ENST00000641840.1	c.*99C>T		3_prime_UTR_variant	2/2		NM_007160.4	ENSP00000492959	P1
GABBR1	ENST00000355973.7	c.*2+14559G>A		intron_variant		2		ENSP00000348248
OR2H2	ENST00000383640.4			downstream_gene_variant				ENSP00000373136	P1

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7584 AN: 152150 Hom.: 251 Cov.: 32

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0533

Gnomad ASJ AF: 0.0841

Gnomad EAS AF: 0.0984

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0281

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0581

Gnomad OTH AF: 0.0606

GnomAD4 exome AF: 0.0665 AC: 33045 AN: 496854 Hom.: 1442 Cov.: 0 AF XY: 0.0710 AC XY: 18738 AN XY: 263804

Gnomad4 AFR exome AF: 0.0216

Gnomad4 AMR exome AF: 0.0680

Gnomad4 ASJ exome AF: 0.0861

Gnomad4 EAS exome AF: 0.0747

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.0259

Gnomad4 NFE exome AF: 0.0601

Gnomad4 OTH exome AF: 0.0694

GnomAD4 genome AF: 0.0498 AC: 7582 AN: 152268 Hom.: 249 Cov.: 32 AF XY: 0.0506 AC XY: 3765 AN XY: 74466

Gnomad4 AFR AF: 0.0215

Gnomad4 AMR AF: 0.0532

Gnomad4 ASJ AF: 0.0841

Gnomad4 EAS AF: 0.0982

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0281

Gnomad4 NFE AF: 0.0581

Gnomad4 OTH AF: 0.0614

Alfa AF: 0.0587 Hom.: 322

Bravo AF: 0.0498

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.098
DANN	Benign	0.49

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: rs362521; hg19: chr6-29556759;