Genetic Variant NM_001004726.1:c.844C>T (chr11-48264704-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.46 ( 18069 hom., cov: 33)

Exomes 𝑓: 0.54 ( 220407 hom. )

Consequence

OR4X1
NM_001004726.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.66

Variant links:

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]

OR4X1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4X1	NM_001004726.1 link	c.844C>T	p.Pro282Ser	missense_variant	Exon 1 of 1	ENST00000320048.1	NP_001004726.1	Q8NH49

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4X1	ENST00000320048.1 link	c.844C>T	p.Pro282Ser	missense_variant	Exon 1 of 1	6	NM_001004726.1	ENSP00000321506.1		Q8NH49

Frequencies

GnomAD3 genomes

AF:

0.458

AC:

69606

AN:

151996

Hom.:

18060

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.521

AC:

130434

AN:

250564

Hom.:

36088

AF XY:

0.515

AC XY:

69681

AN XY:

135386

show subpopulations

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 SAS exome

AF:

0.357

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.:

AF XY:

0.538

AC XY:

390965

AN XY:

726268

show subpopulations

Gnomad4 AFR exome

AF:

0.189

Gnomad4 AMR exome

AF:

0.641

Gnomad4 ASJ exome

AF:

0.552

Gnomad4 EAS exome

AF:

0.463

Gnomad4 SAS exome

AF:

0.362

Gnomad4 FIN exome

AF:

0.603

Gnomad4 NFE exome

AF:

0.565

Gnomad4 OTH exome

AF:

0.513

GnomAD4 genome

AF:

0.458

AC:

69637

AN:

152114

Hom.:

18069

Cov.:

AF XY:

0.457

AC XY:

34019

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.566

Gnomad4 ASJ

AF:

0.544

Gnomad4 EAS

AF:

0.411

Gnomad4 SAS

AF:

0.372

Gnomad4 FIN

AF:

0.607

Gnomad4 NFE

AF:

0.567

Gnomad4 OTH

AF:

0.486

Alfa

AF:

0.543

Hom.:

57528

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.045

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.000019

MetaSVM

Benign

-0.90

MutationAssessor

Pathogenic

3.5

PrimateAI

Benign

0.23

PROVEAN

Pathogenic

-7.2

REVEL

Benign

0.24

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.22

MPC

0.0075

ClinPred

0.042

GERP RS

4.3

Varity_R

0.62

gMVP

0.31

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over