Genetic Variant OR4P4:p.Leu182Trp (chr11-55638902-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001405919.1(OR4P4):c.545T>G(p.Leu182Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,353,476 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 26)

Exomes 𝑓: 0.000016 ( 5 hom. )

Consequence

OR4P4
NM_001405919.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.442

Publications

2 publications found

Variant links:

Genes affected

OR4P4 (HGNC:15180): (olfactory receptor family 4 subfamily P member 4) 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. [provided by RefSeq, Jul 2008]

OR4P4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001405919.1. 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
	OR4P4	NM_001405919.1	MANE Select	c.545T>G	p.Leu182Trp	missense	Exon 2 of 2	NP_001392848.1	Q8NGL7
	OR4P4	NM_001004124.2		c.545T>G	p.Leu182Trp	missense	Exon 1 of 1	NP_001004124.1	Q8NGL7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4P4	ENST00000641760.1	MANE Select	c.545T>G	p.Leu182Trp	missense	Exon 2 of 2	ENSP00000493384.1	Q8NGL7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000441

AC:

AN:

226562

AF XY:

0.00000814

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000957

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000155

AC:

AN:

1353476

Hom.:

Cov.:

AF XY:

0.0000208

AC XY:

AN XY:

673310

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32900

American (AMR)

AF:

0.00

AC:

AN:

37190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24316

East Asian (EAS)

AF:

0.00

AC:

AN:

34568

South Asian (SAS)

AF:

0.00

AC:

AN:

80496

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47668

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5024

European-Non Finnish (NFE)

AF:

0.0000193

AC:

AN:

1035402

Other (OTH)

AF:

0.0000179

AC:

AN:

55912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Uncertain

0.046

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0074

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.0020

MetaRNN

Uncertain

0.57

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

4.0

PhyloP100

0.44

PrimateAI

Benign

0.23

PROVEAN

Pathogenic

-5.9

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.72

MutPred

0.57

Gain of catalytic residue at L182 (P = 0.0034)

MVP

0.84

MPC

0.18

ClinPred

0.92

GERP RS

5.5

Varity_R

0.76

gMVP

0.23

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over