Variant 12-48526034-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001390849.1(OR8S1):c.403A>G(p.Ile135Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OR8S1
NM_001390849.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.320

Variant links:

Genes affected

OR8S1 (HGNC:19628): (olfactory receptor family 8 subfamily S member 1) 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]

OR8S1 links:

ENSG00000197376 (HGNC:):

ENSG00000197376 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058105707).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR8S1	NM_001390849.1 link	c.403A>G	p.Ile135Val	missense_variant	1/1	ENST00000641651.1	NP_001377778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR8S1	ENST00000641651.1 link	c.403A>G	p.Ile135Val	missense_variant	1/1		NM_001390849.1	ENSP00000493379.1		A0A286YFL9
ENSG00000197376	ENST00000551654.1 link	n.184-1838A>G		intron_variant		6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727226

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 20, 2024

The c.403A>G (p.I135V) alteration is located in exon 1 (coding exon 1) of the OR8S1 gene. This alteration results from a A to G substitution at nucleotide position 403, causing the isoleucine (I) at amino acid position 135 to be replaced by a valine (V). 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

0.099

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.11

DANN

Benign

0.81

DEOGEN2

Benign

0.0026

.;T

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

.;L

PrimateAI

Benign

0.20

PROVEAN

Benign

0.17

.;N

REVEL

Benign

0.019

Sift

Benign

0.73

.;T

Sift4G

Benign

0.47

.;T

Polyphen

0.0030

.;B

Vest4

0.016

MutPred

0.39

Gain of catalytic residue at Q139 (P = 0);Gain of catalytic residue at Q139 (P = 0);

MVP

0.099

MPC

0.040

ClinPred

0.034

GERP RS

-0.11

Varity_R

0.033

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over