Variant chr11-55638681-A-G 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.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. 15/21 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_001004124.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -8.97

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=0.009621024).

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 id is 3053908.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4P4	NM_001004124.2 link	c.324A>G	p.Ile108Met	missense_variant	1/1		NP_001004124.1	Q8NGL7
OR4P4	NM_001405919.1 link	c.324A>G	p.Ile108Met	missense_variant	2/2		NP_001392848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR4P4	ENST00000641760.1 link	c.324A>G	p.Ile108Met	missense_variant	2/2			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

GnomAD3 exomes

AF:

0.000136

AC:

AN:

228720

Hom.:

AF XY:

0.000121

AC XY:

AN XY:

123896

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 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:

0.0000695

AC:

AN:

1352838

Hom.:

Cov.:

AF XY:

0.0000877

AC XY:

AN XY:

673124

show subpopulations

Gnomad4 AFR exome

AF:

0.00207

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:

0.000179

GnomAD4 genome

AF:

0.000583

AC:

AN:

138826

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

AN XY:

67424

show subpopulations

Gnomad4 AFR

AF:

0.00170

Gnomad4 AMR

AF:

0.000704

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:

0.00163

Alfa

AF:

0.000491

Hom.:

ESP6500AA

AF:

0.000918

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000193

AC:

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

Benign

0.075

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.8

DANN

Benign

0.96

DEOGEN2

Benign

0.0042

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.32

.;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.0096

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.020

N;N

PrimateAI

Benign

0.18

PROVEAN

Benign

-1.7

.;N

REVEL

Benign

0.12

Sift

Benign

0.13

.;T

Sift4G

Benign

0.32

.;T

Polyphen

0.96

D;D

Vest4

0.16

MVP

0.12

MPC

0.021

ClinPred

0.070

GERP RS

-10

Varity_R

0.15

gMVP

0.076

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

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