Variant 11-55651283-C-T 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.380C>T(p.Pro127Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000104 in 1,346,140 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 25)

Exomes 𝑓: 0.000010 ( 4 hom. )

Consequence

OR4S2
NM_001004059.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4S2	NM_001004059.3 linkuse as main transcript	c.380C>T	p.Pro127Leu	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.380C>T	p.Pro127Leu	missense_variant	2/2		NM_001004059.3	ENSP00000493389.1		Q8NH73

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000656

AC:

AN:

228614

Hom.:

AF XY:

0.0000565

AC XY:

AN XY:

123848

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000522

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1346140

Hom.:

Cov.:

AF XY:

0.0000119

AC XY:

AN XY:

670174

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000374

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000606

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

May 13, 2024

The c.380C>T (p.P127L) alteration is located in exon 1 (coding exon 1) of the OR4S2 gene. This alteration results from a C to T substitution at nucleotide position 380, causing the proline (P) at amino acid position 127 to be replaced by a leucine (L). 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

Uncertain

0.54

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

T;T

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

.;D

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.9

H;H

PrimateAI

Benign

0.25

PROVEAN

Pathogenic

-9.8

.;D

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

.;D

Polyphen

1.0

D;D

Vest4

0.71

MutPred

0.61

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);

MVP

0.55

MPC

0.27

ClinPred

1.0

GERP RS

5.4

Varity_R

0.78

gMVP

0.60

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