Variant chr11-55650946-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001004059.3(OR4S2):c.43C>A(p.Leu15Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 1,464,254 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000022 ( 1 hom., cov: 26)

Exomes 𝑓: 0.0000090 ( 3 hom. )

Consequence

OR4S2
NM_001004059.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.880

Variant links:

Genes affected

OR4S2 (HGNC:15183): (olfactory receptor family 4 subfamily S member 2) 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]

OR4S2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4S2	NM_001004059.3 linkuse as main transcript	c.43C>A	p.Leu15Ile	missense_variant	2/2	ENST00000641692.1	NP_001004059.2	Q8NH73A0A126GVG1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR4S2	ENST00000641692.1 linkuse as main transcript	c.43C>A	p.Leu15Ile	missense_variant	2/2		NM_001004059.3	ENSP00000493389.1		Q8NH73

Frequencies

GnomAD3 genomes

AF:

0.0000217

AC:

AN:

138028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000483

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000883

AC:

AN:

226604

Hom.:

AF XY:

0.0000163

AC XY:

AN XY:

122868

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:

0.0000191

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000905

AC:

AN:

1326226

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

661158

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:

0.0000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000217

AC:

AN:

138028

Hom.:

Cov.:

AF XY:

0.0000448

AC XY:

AN XY:

66910

show subpopulations

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:

0.0000483

Gnomad4 OTH

AF:

0.00

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

Dec 21, 2022

The c.43C>A (p.L15I) alteration is located in exon 1 (coding exon 1) of the OR4S2 gene. This alteration results from a C to A substitution at nucleotide position 43, causing the leucine (L) at amino acid position 15 to be replaced by an isoleucine (I). 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

0.10

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0053

T;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.057

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.67

.;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.7

L;L

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.4

.;N

REVEL

Benign

0.14

Sift

Uncertain

0.010

.;D

Sift4G

Uncertain

0.019

.;D

Polyphen

0.96

D;D

Vest4

0.18

MutPred

0.66

Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);

MVP

0.42

MPC

0.13

ClinPred

0.86

GERP RS

5.3

Varity_R

0.17

gMVP

0.074

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.23

Position offset: -3

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