Variant chr15-22094904-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001005241.4(OR4N4):c.383G>A(p.Arg128Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 4)

Exomes 𝑓: 0.00012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR4N4
NM_001005241.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.704

Variant links:

Genes affected

OR4N4 (HGNC:15375): (olfactory receptor family 4 subfamily N 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]

OR4N4 links:

OR4M2-OT1 (HGNC:):

OR4M2-OT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024115294).

BP6

Variant 15-22094904-G-A is Benign according to our data. Variant chr15-22094904-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3302947.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR4N4	NM_001005241.4 linkuse as main transcript	c.383G>A	p.Arg128Gln	missense_variant	1/1	ENST00000328795.6
OR4M2-OT1	NR_110480.1 linkuse as main transcript	n.1102+113G>A		intron_variant, non_coding_transcript_variant
OR4M2-OT1	NR_110481.1 linkuse as main transcript	n.834+113G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR4N4	ENST00000328795.6 linkuse as main transcript	c.383G>A	p.Arg128Gln	missense_variant	1/1		NM_001005241.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

35178

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000318

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00136

Gnomad EAS

AF:

0.00190

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:

0.000189

AC:

AN:

249112

Hom.:

AF XY:

0.000156

AC XY:

AN XY:

134554

show subpopulations

Gnomad AFR exome

AF:

0.000621

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00150

Gnomad EAS exome

AF:

0.000817

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000445

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000120

AC:

AN:

349738

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

183534

show subpopulations

Gnomad4 AFR exome

AF:

0.000227

Gnomad4 AMR exome

AF:

0.0000933

Gnomad4 ASJ exome

AF:

0.00187

Gnomad4 EAS exome

AF:

0.000566

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000142

Gnomad4 OTH exome

AF:

0.0000502

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000227

AC:

AN:

35236

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

16520

show subpopulations

Gnomad4 AFR

AF:

0.000317

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00136

Gnomad4 EAS

AF:

0.00190

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000193

Hom.:

ESP6500AA

AF:

0.000685

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000149

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000599

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0042

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.70

T;.

M_CAP

Benign

0.0018

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.77

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.5

.;N

REVEL

Benign

0.029

Sift

Benign

0.20

.;T

Sift4G

Benign

0.10

.;T

Polyphen

0.0020

.;B

Vest4

0.055

MVP

0.17

MPC

0.079

ClinPred

0.0046

GERP RS

0.15

Varity_R

0.080

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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