Genetic Variant OR1S2:p.Ile155Val (chr11-58203680-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004459.2(OR1S2):c.463A>G(p.Ile155Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,066 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I155T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

OR1S2
NM_001004459.2 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -0.361

Publications

1 publications found

Variant links:

Genes affected

OR1S2 (HGNC:15141): (olfactory receptor family 1 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]

OR1S2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050008774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR1S2	NM_001004459.2 link	c.463A>G	p.Ile155Val	missense_variant	Exon 1 of 1	ENST00000641683.2	NP_001004459.2	Q8NGQ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR1S2	ENST00000641683.2 link	c.463A>G	p.Ile155Val	missense_variant	Exon 1 of 1		NM_001004459.2	ENSP00000493223.1		A0A286YFI5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152066

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Prostate cancer

Uncertain:1

Science for Life laboratory, Karolinska Institutet

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.8

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.0016

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.15

T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.10

.;N

PhyloP100

-0.36

PROVEAN

Benign

0.16

.;N

REVEL

Benign

0.022

Sift

Benign

0.61

.;T

Sift4G

Benign

0.56

.;T

Polyphen

0.0010

.;B

Vest4

0.024

MutPred

0.34

.;Gain of catalytic residue at I168 (P = 0.0568);

MVP

0.24

MPC

0.0053

ClinPred

0.026

GERP RS

2.4

PromoterAI

0.0028

Neutral

(source)

Varity_R

0.048

gMVP

0.041

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over