6-29555869-G-C

Variant names:

• chr6-29555869-G-C
• rs444013
• NM_001396058.1:c.*1703G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001396058.1(OR2I1):​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: OR2I1 NM_001396058.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 14 publications found

Genes affected

OR2I1 (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]

GABBR1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with language delay and variable cognitive abnormalities

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OR2I1	NM_001396058.1	c.*1703G>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000641137.2	NP_001382987.1
UBD	NM_006398.4	c.*11C>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000377050.5	NP_006389.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2I1P	ENST00000641137.2	c.*1703G>C		3_prime_UTR_variant	Exon 2 of 2		NM_001396058.1	ENSP00000493715.1
UBD	ENST00000377050.5	c.*11C>G		3_prime_UTR_variant	Exon 2 of 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

GnomAD2 exomes AF: 0.612 AC: 150292 AN: 245670 AF XY: 0.615

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 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

African (AFR) AF: 0.743 AC: 24744 AN: 33292

American (AMR) AF: 0.612 AC: 27343 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 12943 AN: 26034

East Asian (EAS) AF: 0.717 AC: 28461 AN: 39670

South Asian (SAS) AF: 0.760 AC: 65411 AN: 86052

European-Finnish (FIN) AF: 0.616 AC: 32087 AN: 52058

Middle Eastern (MID) AF: 0.615 AC: 3544 AN: 5758

European-Non Finnish (NFE) AF: 0.517 AC: 572395 AN: 1106284

Other (OTH) AF: 0.568 AC: 34181 AN: 60130

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

African (AFR) AF: 0.742 AC: 30784 AN: 41478

American (AMR) AF: 0.585 AC: 8943 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1699 AN: 3472

East Asian (EAS) AF: 0.756 AC: 3908 AN: 5170

South Asian (SAS) AF: 0.785 AC: 3777 AN: 4810

European-Finnish (FIN) AF: 0.621 AC: 6545 AN: 10546

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36193 AN: 67954

Other (OTH) AF: 0.624 AC: 1317 AN: 2110

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
PhyloP100		0.086
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs444013; hg19: chr6-29523646;