chr6-29555869-G-C

Position:

• chr6-29555869-G-C

Variant summary

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

The NM_001396058.1(OR2I1P):​c.*1703G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,605,994 control chromosomes in the GnomAD database, including 255,129 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 0.62 (29560 hom., cov: 32)
  • Exomes 𝑓: 0.55 (225569 hom.)
• Consequence: OR2I1P NM_001396058.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

Genes affected

OR2I1P (HGNC:8258): (olfactory receptor family 2 subfamily I member 1 pseudogene) 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]

UBD (HGNC:18795): (ubiquitin D) This gene encodes a protein which contains two ubiquitin-like domains and appears to have similar function to ubiquitin. Through covalent attachment, the encoded protein targets other proteins for 26S proteasome degradation. This protein has been implicated to function in many cellular processes, including caspase-dependent apoptosis, formation of aggresomes, mitotic regulation, and dendritic cell maturation. Upregulation of this gene may promote inflammation in chronic kidney disease and has been observed in many cancer types. [provided by RefSeq, Aug 2017]

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]

OR2I1P (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2I1P	NM_001396058.1	c.*1703G>C		3_prime_UTR_variant	2/2	ENST00000641137.2	NP_001382987.1
UBD	NM_006398.4	c.*11C>G		3_prime_UTR_variant	2/2	ENST00000377050.5	NP_006389.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2I1P	ENST00000641137.2	c.*1703G>C		3_prime_UTR_variant	2/2		NM_001396058.1	ENSP00000493715.1
UBD	ENST00000377050.5	c.*11C>G		3_prime_UTR_variant	2/2	1	NM_006398.4	ENSP00000366249.4

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93621 AN: 151904 Hom.: 29513 Cov.: 32

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.620

GnomAD3 exomes AF: 0.612 AC: 150292 AN: 245670 Hom.: 47112 AF XY: 0.615 AC XY: 82264 AN XY: 133866

Gnomad AFR exome AF: 0.746

Gnomad AMR exome AF: 0.617

Gnomad ASJ exome AF: 0.502

Gnomad EAS exome AF: 0.752

Gnomad SAS exome AF: 0.760

Gnomad FIN exome AF: 0.619

Gnomad NFE exome AF: 0.538

Gnomad OTH exome AF: 0.590

GnomAD4 exome AF: 0.551 AC: 801109 AN: 1453972 Hom.: 225569 Cov.: 30 AF XY: 0.556 AC XY: 402321 AN XY: 723418

Gnomad4 AFR exome AF: 0.743

Gnomad4 AMR exome AF: 0.612

Gnomad4 ASJ exome AF: 0.497

Gnomad4 EAS exome AF: 0.717

Gnomad4 SAS exome AF: 0.760

Gnomad4 FIN exome AF: 0.616

Gnomad4 NFE exome AF: 0.517

Gnomad4 OTH exome AF: 0.568

GnomAD4 genome AF: 0.617 AC: 93723 AN: 152022 Hom.: 29560 Cov.: 32 AF XY: 0.623 AC XY: 46272 AN XY: 74284

Gnomad4 AFR AF: 0.742

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.785

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.624

Alfa AF: 0.559 Hom.: 4446

Bravo AF: 0.620

Asia WGS AF: 0.787 AC: 2735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.4
DANN	Benign	0.38

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: rs444013; hg19: chr6-29523646;