Genetic Variant ENST00000641760.1:c.352T>C (chr11-55638709-T-C) – ACMG Classification: Benign (-9 pts)

Variant summary

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

The ENST00000641760.1(OR4P4):c.352T>C(p.Tyr118His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,491,790 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00060 ( 12 hom., cov: 25)

Exomes 𝑓: 0.000072 ( 17 hom. )

Consequence

OR4P4
ENST00000641760.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.20

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012865722).

BP6

Variant 11-55638709-T-C is Benign according to our data. Variant chr11-55638709-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3054240.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000641760.1. 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.352T>C	p.Tyr118His	missense	Exon 2 of 2	NP_001392848.1	Q8NGL7
	OR4P4	NM_001004124.2		c.352T>C	p.Tyr118His	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.352T>C	p.Tyr118His	missense	Exon 2 of 2	ENSP00000493384.1	Q8NGL7

Frequencies

GnomAD3 genomes

AF:

0.000598

AC:

AN:

138852

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00175

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:

0.00347

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00164

GnomAD2 exomes

AF:

0.000127

AC:

AN:

228198

AF XY:

0.000121

show subpopulations

Gnomad AFR exome

AF:

0.00156

Gnomad AMR exome

AF:

0.000140

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:

0.0000717

AC:

AN:

1352852

Hom.:

Cov.:

AF XY:

0.0000877

AC XY:

AN XY:

672996

show subpopulations

African (AFR)

AF:

0.00213

AC:

AN:

32882

American (AMR)

AF:

0.000187

AC:

AN:

37352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24396

East Asian (EAS)

AF:

0.00

AC:

AN:

34550

South Asian (SAS)

AF:

0.00

AC:

AN:

80666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48108

Middle Eastern (MID)

AF:

0.000796

AC:

AN:

5028

European-Non Finnish (NFE)

AF:

0.00000484

AC:

AN:

1033934

Other (OTH)

AF:

0.000197

AC:

AN:

55936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

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:

0.000597

AC:

AN:

138938

Hom.:

Cov.:

AF XY:

0.000563

AC XY:

AN XY:

67530

show subpopulations

African (AFR)

AF:

0.00175

AC:

AN:

40014

American (AMR)

AF:

0.000703

AC:

AN:

12800

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3224

East Asian (EAS)

AF:

0.00

AC:

AN:

4230

South Asian (SAS)

AF:

0.00

AC:

AN:

4280

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9070

Middle Eastern (MID)

AF:

0.00376

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62396

Other (OTH)

AF:

0.00164

AC:

AN:

1834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.000917

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000194

AC:

Asia WGS

AF:

0.00161

AC:

AN:

3122

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

Uncertain

0.37

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.78

M_CAP

Benign

0.0028

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.7

PhyloP100

2.2

PrimateAI

Benign

0.23

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.12

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.0020

Polyphen

0.13

Vest4

0.36

MVP

0.14

MPC

0.031

ClinPred

0.088

GERP RS

4.2

Varity_R

0.62

gMVP

0.15

Mutation Taster

=98/2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over