11-48264704-C-T

Variant names:

• chr11-48264704-C-T
• rs10838852
• NM_001004726.1:c.844C>T

Variant summary

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

The NM_001004726.1(OR4X1):​c.844C>T​(p.Pro282Ser) variant causes a missense change. The variant allele was found at a frequency of 0.535 in 1,611,784 control chromosomes in the GnomAD database, including 238,476 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 0.46 (18069 hom., cov: 33)
  • Exomes 𝑓: 0.54 (220407 hom.)
• Consequence: OR4X1 NM_001004726.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.66
• Publications: 34 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.8911669E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.562 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4X1	NM_001004726.1	MANE Select	c.844C>T	p.Pro282Ser	missense	Exon 1 of 1	NP_001004726.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4X1	ENST00000320048.1	TSL:6 MANE Select	c.844C>T	p.Pro282Ser	missense	Exon 1 of 1	ENSP00000321506.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69606 AN: 151996 Hom.: 18060 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.483

GnomAD2 exomes AF: 0.521 AC: 130434 AN: 250564 AF XY: 0.515

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.650

Gnomad ASJ exome AF: 0.553

Gnomad EAS exome AF: 0.411

Gnomad FIN exome AF: 0.605

Gnomad NFE exome AF: 0.569

Gnomad OTH exome AF: 0.553

GnomAD4 exome AF: 0.543 AC: 791998 AN: 1459670 Hom.: 220407 Cov.: 35 AF XY: 0.538 AC XY: 390965 AN XY: 726268

African (AFR) AF: 0.189 AC: 6317 AN: 33450

American (AMR) AF: 0.641 AC: 28656 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 14420 AN: 26116

East Asian (EAS) AF: 0.463 AC: 18351 AN: 39672

South Asian (SAS) AF: 0.362 AC: 31218 AN: 86204

European-Finnish (FIN) AF: 0.603 AC: 32208 AN: 53390

Middle Eastern (MID) AF: 0.484 AC: 2791 AN: 5764

European-Non Finnish (NFE) AF: 0.565 AC: 627103 AN: 1110046

Other (OTH) AF: 0.513 AC: 30934 AN: 60328

GnomAD4 genome AF: 0.458 AC: 69637 AN: 152114 Hom.: 18069 Cov.: 33 AF XY: 0.457 AC XY: 34019 AN XY: 74370

African (AFR) AF: 0.202 AC: 8402 AN: 41496

American (AMR) AF: 0.566 AC: 8638 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1884 AN: 3464

East Asian (EAS) AF: 0.411 AC: 2126 AN: 5174

South Asian (SAS) AF: 0.372 AC: 1797 AN: 4826

European-Finnish (FIN) AF: 0.607 AC: 6424 AN: 10576

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38531 AN: 67994

Other (OTH) AF: 0.486 AC: 1027 AN: 2112

Alfa AF: 0.527 Hom.: 75335

Bravo AF: 0.450

TwinsUK AF: 0.562 AC: 2083

ALSPAC AF: 0.569 AC: 2194

ESP6500AA AF: 0.218 AC: 959

ESP6500EA AF: 0.566 AC: 4869

ExAC AF: 0.512 AC: 62145

Asia WGS AF: 0.358 AC: 1245 AN: 3476

EpiCase AF: 0.560

EpiControl AF: 0.558

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T
Eigen	Pathogenic	0.74
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.000019	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		4.7
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.22
MPC		0.0075
ClinPred		0.042	T
GERP RS		4.3
Varity_R		0.62
gMVP		0.31
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10838852; hg19: chr11-48286256; COSMIC: COSV60723428;