Genetic Variant OR4P4:p.Ala35Val (chr11-55638461-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001405919.1(OR4P4):c.104C>T(p.Ala35Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,465,808 control chromosomes in the GnomAD database, including 41 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000058 ( 1 hom., cov: 25)

Exomes 𝑓: 0.00015 ( 40 hom. )

Consequence

OR4P4
NM_001405919.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.00

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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008223385).

BS2

High Homozygotes in GnomAdExome4 at 40 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.104C>T	p.Ala35Val	missense	Exon 2 of 2	NP_001392848.1	Q8NGL7
	OR4P4	NM_001004124.2		c.104C>T	p.Ala35Val	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.104C>T	p.Ala35Val	missense	Exon 2 of 2	ENSP00000493384.1	Q8NGL7

Frequencies

GnomAD3 genomes

AF:

0.0000581

AC:

AN:

137652

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000161

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000282

AC:

AN:

226678

AF XY:

0.000309

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000354

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000193

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000669

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000153

AC:

203

AN:

1328156

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

133

AN XY:

662186

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32614

American (AMR)

AF:

0.0000271

AC:

AN:

36926

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24130

East Asian (EAS)

AF:

0.0000871

AC:

AN:

34430

South Asian (SAS)

AF:

0.00213

AC:

170

AN:

79924

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47880

Middle Eastern (MID)

AF:

0.00101

AC:

AN:

4962

European-Non Finnish (NFE)

AF:

0.0000168

AC:

AN:

1012268

Other (OTH)

AF:

0.000127

AC:

AN:

55022

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

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:

0.0000581

AC:

AN:

137652

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

66700

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39610

American (AMR)

AF:

0.00

AC:

AN:

12590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3186

East Asian (EAS)

AF:

0.00

AC:

AN:

4198

South Asian (SAS)

AF:

0.00166

AC:

AN:

4214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8850

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0000161

AC:

AN:

62076

Other (OTH)

AF:

0.00

AC:

AN:

1834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.0000843

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000124

AC:

ExAC

AF:

0.000280

AC:

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

Benign

0.12

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.6

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0049

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.69

M_CAP

Benign

0.0016

MetaRNN

Benign

0.0082

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.010

PhyloP100

-1.0

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.4

REVEL

Benign

0.034

Sift

Benign

0.33

Sift4G

Benign

0.54

Polyphen

0.054

Vest4

0.083

MVP

0.14

MPC

0.020

ClinPred

0.017

GERP RS

0.68

Varity_R

0.048

gMVP

0.052

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over