11-48264679-T-A

Variant names:

• chr11-48264679-T-A
• rs10838851
• NM_001004726.1:c.819T>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001004726.1(OR4X1):​c.819T>A​(p.Tyr273*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,613,266 control chromosomes in the GnomAD database, including 435,620 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (36959 hom., cov: 33)
  • Exomes 𝑓: 0.73 (398661 hom.)
• Consequence: OR4X1 NM_001004726.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 46 publications found

Genes affected

OR4X1 (HGNC:14854): (olfactory receptor family 4 subfamily X member 1) 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, Jul 2015]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004726.1. 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
	OR4X1	NM_001004726.1	MANE Select	c.819T>A	p.Tyr273*	stop_gained	Exon 1 of 1	NP_001004726.1	Q8NH49

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4X1	ENST00000320048.1	TSL:6 MANE Select	c.819T>A	p.Tyr273*	stop_gained	Exon 1 of 1	ENSP00000321506.1	Q8NH49

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104863 AN: 152022 Hom.: 36946 Cov.: 33

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.679

GnomAD2 exomes AF: 0.710 AC: 178267 AN: 250956 AF XY: 0.701

Gnomad AFR exome AF: 0.556

Gnomad AMR exome AF: 0.808

Gnomad ASJ exome AF: 0.696

Gnomad EAS exome AF: 0.581

Gnomad FIN exome AF: 0.799

Gnomad NFE exome AF: 0.756

Gnomad OTH exome AF: 0.717

GnomAD4 exome AF: 0.735 AC: 1073912 AN: 1461126 Hom.: 398661 Cov.: 40 AF XY: 0.729 AC XY: 530178 AN XY: 726918

African (AFR) AF: 0.550 AC: 18409 AN: 33464

American (AMR) AF: 0.800 AC: 35757 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 18082 AN: 26122

East Asian (EAS) AF: 0.628 AC: 24916 AN: 39680

South Asian (SAS) AF: 0.541 AC: 46680 AN: 86242

European-Finnish (FIN) AF: 0.793 AC: 42375 AN: 53412

Middle Eastern (MID) AF: 0.636 AC: 3665 AN: 5766

European-Non Finnish (NFE) AF: 0.757 AC: 841777 AN: 1111348

Other (OTH) AF: 0.700 AC: 42251 AN: 60368

GnomAD4 genome AF: 0.690 AC: 104914 AN: 152140 Hom.: 36959 Cov.: 33 AF XY: 0.689 AC XY: 51251 AN XY: 74382

African (AFR) AF: 0.559 AC: 23158 AN: 41454

American (AMR) AF: 0.737 AC: 11267 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2406 AN: 3470

East Asian (EAS) AF: 0.578 AC: 2984 AN: 5164

South Asian (SAS) AF: 0.545 AC: 2633 AN: 4830

European-Finnish (FIN) AF: 0.811 AC: 8600 AN: 10604

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51468 AN: 68006

Other (OTH) AF: 0.679 AC: 1437 AN: 2116

Alfa AF: 0.735 Hom.: 13412

Bravo AF: 0.682

TwinsUK AF: 0.767 AC: 2845

ALSPAC AF: 0.766 AC: 2951

ESP6500AA AF: 0.566 AC: 2491

ESP6500EA AF: 0.755 AC: 6486

ExAC AF: 0.704 AC: 85411

Asia WGS AF: 0.514 AC: 1787 AN: 3476

EpiCase AF: 0.738

EpiControl AF: 0.729

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	34
DANN	Uncertain	0.98
Eigen	Benign	-0.014
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.22	N
PhyloP100		-1.3
Vest4		0.12
GERP RS		2.4
Mutation Taster		=173/27	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: rs10838851; hg19: chr11-48286231; COSMIC: COSV60723080;