NM_001004744.1:c.550T>C

Variant names:

• chr11-56417683-A-G
• rs7930678
• NM_001004744.1:c.550T>C

Variant summary

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

The NM_001004744.1(OR8U3):​c.550T>C​(p.Phe184Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,613,504 control chromosomes in the GnomAD database, including 62,080 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8972 hom., cov: 32)
  • Exomes 𝑓: 0.26 (53108 hom.)
• Consequence: OR8U3 NM_001004744.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• Publications: 30 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=5.1442163E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004744.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR8U3	NM_001004744.1	MANE Select	c.550T>C	p.Phe184Leu	missense	Exon 1 of 1	NP_001004744.1	Q8NH85

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR8U3	ENST00000623286.1	TSL:6 MANE Select	c.550T>C	p.Phe184Leu	missense	Exon 1 of 1	ENSP00000485324.1	Q8NH85

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48646 AN: 151884 Hom.: 8962 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.306

GnomAD2 exomes AF: 0.249 AC: 62519 AN: 251032 AF XY: 0.246

Gnomad AFR exome AF: 0.517

Gnomad AMR exome AF: 0.160

Gnomad ASJ exome AF: 0.355

Gnomad EAS exome AF: 0.117

Gnomad FIN exome AF: 0.193

Gnomad NFE exome AF: 0.271

Gnomad OTH exome AF: 0.256

GnomAD4 exome AF: 0.263 AC: 384773 AN: 1461502 Hom.: 53108 Cov.: 42 AF XY: 0.261 AC XY: 189970 AN XY: 727056

African (AFR) AF: 0.521 AC: 17429 AN: 33454

American (AMR) AF: 0.164 AC: 7340 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 9216 AN: 26126

East Asian (EAS) AF: 0.130 AC: 5159 AN: 39696

South Asian (SAS) AF: 0.206 AC: 17749 AN: 86254

European-Finnish (FIN) AF: 0.200 AC: 10704 AN: 53416

Middle Eastern (MID) AF: 0.280 AC: 1616 AN: 5768

European-Non Finnish (NFE) AF: 0.269 AC: 299262 AN: 1111738

Other (OTH) AF: 0.270 AC: 16298 AN: 60376

GnomAD4 genome AF: 0.320 AC: 48693 AN: 152002 Hom.: 8972 Cov.: 32 AF XY: 0.312 AC XY: 23149 AN XY: 74314

African (AFR) AF: 0.510 AC: 21111 AN: 41408

American (AMR) AF: 0.213 AC: 3252 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1241 AN: 3462

East Asian (EAS) AF: 0.134 AC: 693 AN: 5164

South Asian (SAS) AF: 0.194 AC: 934 AN: 4824

European-Finnish (FIN) AF: 0.193 AC: 2039 AN: 10582

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18384 AN: 67982

Other (OTH) AF: 0.304 AC: 640 AN: 2108

Alfa AF: 0.285 Hom.: 18314

Bravo AF: 0.332

TwinsUK AF: 0.268 AC: 993

ALSPAC AF: 0.273 AC: 1051

ESP6500AA AF: 0.500 AC: 2202

ESP6500EA AF: 0.279 AC: 2395

ExAC AF: 0.257 AC: 31191

Asia WGS AF: 0.169 AC: 592 AN: 3478

EpiCase AF: 0.266

EpiControl AF: 0.274

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	14
DANN	Benign	0.61
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.000051	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-2.8	N
PhyloP100		-0.14
PrimateAI	Benign	0.23	T
Polyphen		0.0	B
MutPred		0.17		Loss of catalytic residue at C179 (P = 0.1699)
ClinPred		0.0014	T
GERP RS		2.7
Varity_R		0.092
gMVP		0.031
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: rs7930678; hg19: chr11-56185159; COSMIC: COSV56572305; COSMIC: COSV56572305;