Variant 11-55638731-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_001004124.2(OR4P4):c.374G>A(p.Cys125Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000128 in 1,492,464 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000036 ( 1 hom., cov: 25)

Exomes 𝑓: 0.00014 ( 35 hom. )

Consequence

OR4P4
NM_001004124.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.69

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 -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.772

BS2

High Homozygotes in GnomAdExome4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4P4	NM_001004124.2 linkuse as main transcript	c.374G>A	p.Cys125Tyr	missense_variant	1/1		NP_001004124.1	Q8NGL7
OR4P4	NM_001405919.1 linkuse as main transcript	c.374G>A	p.Cys125Tyr	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.374G>A	p.Cys125Tyr	missense_variant	2/2			ENSP00000493384.1		Q8NGL7

Frequencies

GnomAD3 genomes

AF:

0.0000361

AC:

AN:

138598

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000252

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000641

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000132

AC:

AN:

227018

Hom.:

AF XY:

0.0000163

AC XY:

AN XY:

122976

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000287

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000137

AC:

186

AN:

1353866

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

673412

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.000173

Gnomad4 OTH exome

AF:

0.000125

GnomAD4 genome

AF:

0.0000361

AC:

AN:

138598

Hom.:

Cov.:

AF XY:

0.0000446

AC XY:

AN XY:

67274

show subpopulations

Gnomad4 AFR

AF:

0.0000252

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000641

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000177

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

Oct 06, 2024

The c.374G>A (p.C125Y) alteration is located in exon 1 (coding exon 1) of the OR4P4 gene. This alteration results from a G to A substitution at nucleotide position 374, causing the cysteine (C) at amino acid position 125 to be replaced by a tyrosine (Y). 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

0.33

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

.;T

M_CAP

Benign

0.010

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.7

M;M

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-10

.;D

REVEL

Benign

0.29

Sift

Uncertain

0.0090

.;D

Sift4G

Uncertain

0.0050

.;D

Polyphen

1.0

D;D

Vest4

0.50

MutPred

0.50

Gain of catalytic residue at I124 (P = 0.0519);Gain of catalytic residue at I124 (P = 0.0519);

MVP

0.66

MPC

0.18

ClinPred

1.0

GERP RS

4.5

Varity_R

0.66

gMVP

0.16

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