Variant 11-55638709-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001004124.2(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
NM_001004124.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.20

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 made for transcript

Verdict is Benign. Variant got -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 id is 3054240.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4P4	NM_001004124.2 linkuse as main transcript	c.352T>C	p.Tyr118His	missense_variant	1/1		NP_001004124.1	Q8NGL7
OR4P4	NM_001405919.1 linkuse as main transcript	c.352T>C	p.Tyr118His	missense_variant	2/2		NP_001392848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR4P4	ENST00000641760.1 linkuse as main transcript	c.352T>C	p.Tyr118His	missense_variant	2/2			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

GnomAD3 exomes

AF:

0.000127

AC:

AN:

228198

Hom.:

AF XY:

0.000121

AC XY:

AN XY:

123624

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 SAS 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

Gnomad4 AFR exome

AF:

0.00213

Gnomad4 AMR exome

AF:

0.000187

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000484

Gnomad4 OTH exome

AF:

0.000197

GnomAD4 genome

AF:

0.000597

AC:

AN:

138938

Hom.:

Cov.:

AF XY:

0.000563

AC XY:

AN XY:

67530

show subpopulations

Gnomad4 AFR

AF:

0.00175

Gnomad4 AMR

AF:

0.000703

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00164

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

OR4P4-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 27, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.78

.;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.7

M;M

PrimateAI

Benign

0.23

PROVEAN

Pathogenic

-4.5

.;D

REVEL

Benign

0.12

Sift

Uncertain

0.0090

.;D

Sift4G

Uncertain

0.0020

.;D

Polyphen

0.13

B;B

Vest4

0.36

MVP

0.14

MPC

0.031

ClinPred

0.088

GERP RS

4.2

Varity_R

0.62

gMVP

0.15

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over