Genetic Variant OR4P4:p.Ile108Met (chr11-55638681-A-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001405919.1(OR4P4):c.324A>G(p.Ile108Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,491,664 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00058 ( 11 hom., cov: 26)

Exomes 𝑓: 0.000069 ( 16 hom. )

Consequence

OR4P4
NM_001405919.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -8.97

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009621024).

BP6

Variant 11-55638681-A-G is Benign according to our data. Variant chr11-55638681-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3053908.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 11 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.324A>G	p.Ile108Met	missense	Exon 2 of 2	NP_001392848.1	Q8NGL7
	OR4P4	NM_001004124.2		c.324A>G	p.Ile108Met	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.324A>G	p.Ile108Met	missense	Exon 2 of 2	ENSP00000493384.1	Q8NGL7

Frequencies

GnomAD3 genomes

AF:

0.000584

AC:

AN:

138744

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000704

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00355

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00164

GnomAD2 exomes

AF:

0.000136

AC:

AN:

228720

AF XY:

0.000121

show subpopulations

Gnomad AFR exome

AF:

0.00169

Gnomad AMR exome

AF:

0.000139

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000695

AC:

AN:

1352838

Hom.:

Cov.:

AF XY:

0.0000877

AC XY:

AN XY:

673124

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

32886

American (AMR)

AF:

0.000187

AC:

AN:

37386

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24438

East Asian (EAS)

AF:

0.00

AC:

AN:

34556

South Asian (SAS)

AF:

0.00

AC:

AN:

80672

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48138

Middle Eastern (MID)

AF:

0.000794

AC:

AN:

5036

European-Non Finnish (NFE)

AF:

0.00000484

AC:

AN:

1033780

Other (OTH)

AF:

0.000179

AC:

AN:

55946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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

AF:

0.000583

AC:

AN:

138826

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

AN XY:

67424

show subpopulations

African (AFR)

AF:

0.00170

AC:

AN:

40066

American (AMR)

AF:

0.000704

AC:

AN:

12788

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3212

East Asian (EAS)

AF:

0.00

AC:

AN:

4226

South Asian (SAS)

AF:

0.00

AC:

AN:

4286

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8996

Middle Eastern (MID)

AF:

0.00382

AC:

AN:

262

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62336

Other (OTH)

AF:

0.00163

AC:

AN:

1836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000491

Hom.:

ESP6500AA

AF:

0.000918

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000193

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

OR4P4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.8

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0042

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.32

M_CAP

Benign

0.0018

MetaRNN

Benign

0.0096

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.020

PhyloP100

-9.0

PrimateAI

Benign

0.18

PROVEAN

Benign

-1.7

REVEL

Benign

0.12

Sift

Benign

0.13

Sift4G

Benign

0.32

Polyphen

0.96

Vest4

0.16

MVP

0.12

MPC

0.021

ClinPred

0.070

GERP RS

-10

Varity_R

0.15

gMVP

0.076

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over