Variant 15-22094704-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001005241.4(OR4N4):c.183A>C(p.Leu61Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR4N4
NM_001005241.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.876

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015949607).

BP6

Variant 15-22094704-A-C is Benign according to our data. Variant chr15-22094704-A-C is described in ClinVar as [Benign]. Clinvar id is 769404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR4N4	NM_001005241.4 linkuse as main transcript	c.183A>C	p.Leu61Phe	missense_variant	1/1	ENST00000328795.6
OR4M2-OT1	NR_110480.1 linkuse as main transcript	n.1015A>C		non_coding_transcript_exon_variant	8/9
OR4M2-OT1	NR_110481.1 linkuse as main transcript	n.747A>C		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR4N4	ENST00000328795.6 linkuse as main transcript	c.183A>C	p.Leu61Phe	missense_variant	1/1		NM_001005241.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

716

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.186

AC:

40418

AN:

217600

Hom.:

1634

AF XY:

0.182

AC XY:

21364

AN XY:

117264

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.114

Gnomad ASJ exome

AF:

0.215

Gnomad EAS exome

AF:

0.146

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.234

Gnomad NFE exome

AF:

0.209

Gnomad OTH exome

AF:

0.203

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000105

AC:

AN:

76134

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

39522

show subpopulations

Gnomad4 AFR exome

AF:

0.000472

Gnomad4 AMR exome

AF:

0.000397

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:

0.0000943

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

716

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

336

Gnomad4 AFR

AF:

0.00

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.139

Hom.:

226

ExAC

AF:

0.210

AC:

25447

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 23, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.0026

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.28

T;.

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.4

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

5.3

.;N

REVEL

Benign

0.097

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

.;T

Polyphen

0.0

.;B

Vest4

0.044

MutPred

0.38

Gain of catalytic residue at L61 (P = 0.1992);Gain of catalytic residue at L61 (P = 0.1992);

MPC

0.074

ClinPred

0.0033

GERP RS

2.3

Varity_R

0.039

gMVP

0.079

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