rs7111634

Variant names:

• chr11-56417871-T-C
• rs7111634
• NM_001004744.1:c.362A>G

Variant summary

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

The NM_001004744.1(OR8U3):​c.362A>G​(p.Asp121Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 1,613,608 control chromosomes in the GnomAD database, including 5,011 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D121N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.058 (379 hom., cov: 32)
  • Exomes 𝑓: 0.075 (4632 hom.)
• Consequence: OR8U3 NM_001004744.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.95
• Publications: 21 publications found

Genes affected

OR8U3 (HGNC:14841): (olfactory receptor family 8 subfamily U member 3) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032057762).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR8U3	NM_001004744.1	c.362A>G	p.Asp121Gly	missense_variant	Exon 1 of 1	ENST00000623286.1	NP_001004744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR8U3	ENST00000623286.1	c.362A>G	p.Asp121Gly	missense_variant	Exon 1 of 1	6	NM_001004744.1	ENSP00000485324.1

Frequencies

GnomAD3 genomes AF: 0.0579 AC: 8807 AN: 152024 Hom.: 379 Cov.: 32

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0468

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0569

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0834

Gnomad OTH AF: 0.0646

GnomAD2 exomes AF: 0.0643 AC: 16135 AN: 251040 AF XY: 0.0660

Gnomad AFR exome AF: 0.0117

Gnomad AMR exome AF: 0.0323

Gnomad ASJ exome AF: 0.0252

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.131

Gnomad NFE exome AF: 0.0857

Gnomad OTH exome AF: 0.0747

GnomAD4 exome AF: 0.0750 AC: 109633 AN: 1461466 Hom.: 4632 Cov.: 35 AF XY: 0.0747 AC XY: 54283 AN XY: 727052

African (AFR) AF: 0.0114 AC: 380 AN: 33472

American (AMR) AF: 0.0337 AC: 1506 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0252 AC: 659 AN: 26120

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39688

South Asian (SAS) AF: 0.0516 AC: 4453 AN: 86254

European-Finnish (FIN) AF: 0.135 AC: 7192 AN: 53404

Middle Eastern (MID) AF: 0.0617 AC: 356 AN: 5766

European-Non Finnish (NFE) AF: 0.0816 AC: 90750 AN: 1111686

Other (OTH) AF: 0.0717 AC: 4332 AN: 60378

GnomAD4 genome AF: 0.0579 AC: 8803 AN: 152142 Hom.: 379 Cov.: 32 AF XY: 0.0584 AC XY: 4342 AN XY: 74392

African (AFR) AF: 0.0128 AC: 532 AN: 41526

American (AMR) AF: 0.0467 AC: 713 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0282 AC: 98 AN: 3470

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5160

South Asian (SAS) AF: 0.0572 AC: 275 AN: 4810

European-Finnish (FIN) AF: 0.125 AC: 1321 AN: 10592

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0833 AC: 5667 AN: 67998

Other (OTH) AF: 0.0639 AC: 135 AN: 2112

Alfa AF: 0.0695 Hom.: 1163

Bravo AF: 0.0493

TwinsUK AF: 0.0744 AC: 276

ALSPAC AF: 0.0812 AC: 313

ESP6500AA AF: 0.0127 AC: 56

ESP6500EA AF: 0.0808 AC: 694

ExAC AF: 0.0654 AC: 7944

Asia WGS AF: 0.0300 AC: 106 AN: 3478

EpiCase AF: 0.0816

EpiControl AF: 0.0796

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		7.9
PrimateAI	Benign	0.29	T
Polyphen		1.0	D
ClinPred		0.079	T
GERP RS		5.8
PromoterAI		-0.037	Neutral
Varity_R		0.65
gMVP		0.37
Mutation Taster		=64/36	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: rs7111634; hg19: chr11-56185347; COSMIC: COSV56571901; COSMIC: COSV56571901;