Variant 11-55638931-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001405919.1(OR4P4):c.574A>C(p.Met192Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,486,458 control chromosomes in the GnomAD database, including 2 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000029 ( 1 hom., cov: 26)

Exomes 𝑓: 0.0000082 ( 1 hom. )

Consequence

OR4P4
NM_001405919.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.44

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031106085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR4P4	NM_001405919.1 linkuse as main transcript	c.574A>C	p.Met192Leu	missense_variant	2/2	ENST00000641760.1
OR4P4	NM_001004124.2 linkuse as main transcript	c.574A>C	p.Met192Leu	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR4P4	ENST00000641760.1 linkuse as main transcript	c.574A>C	p.Met192Leu	missense_variant	2/2		NM_001405919.1	P1

Frequencies

GnomAD3 genomes

AF:

0.0000288

AC:

AN:

139006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000311

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000179

AC:

AN:

223688

Hom.:

AF XY:

0.00000825

AC XY:

AN XY:

121156

show subpopulations

Gnomad AFR exome

AF:

0.000250

Gnomad AMR exome

AF:

0.00

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:

0.00000816

AC:

AN:

1347452

Hom.:

Cov.:

AF XY:

0.0000104

AC XY:

AN XY:

670386

show subpopulations

Gnomad4 AFR exome

AF:

0.000153

Gnomad4 AMR exome

AF:

0.0000545

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:

0.00

Gnomad4 OTH exome

AF:

0.0000718

GnomAD4 genome

AF:

0.0000288

AC:

AN:

139006

Hom.:

Cov.:

AF XY:

0.0000148

AC XY:

AN XY:

67444

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000311

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:

0.00

Alfa

AF:

0.0000339

Hom.:

ESP6500AA

AF:

0.000459

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000355

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.574A>C (p.M192L) alteration is located in exon 1 (coding exon 1) of the OR4P4 gene. This alteration results from a A to C substitution at nucleotide position 574, causing the methionine (M) at amino acid position 192 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.012

DANN

Benign

0.32

DEOGEN2

Benign

0.0016

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.21

.;T

M_CAP

Benign

0.0010

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.8

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.18

PROVEAN

Benign

0.14

.;N

REVEL

Benign

0.019

Sift

Benign

0.68

.;T

Sift4G

Benign

0.50

.;T

Polyphen

0.0

B;B

Vest4

0.052

MutPred

0.14

Gain of catalytic residue at M192 (P = 0.1627);Gain of catalytic residue at M192 (P = 0.1627);

MVP

0.14

MPC

0.019

ClinPred

0.020

GERP RS

-5.3

Varity_R

0.054

gMVP

0.10

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