Variant chr11-55651135-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001004059.3(OR4S2):c.232A>G(p.Lys78Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000577 in 1,473,850 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 5 hom., cov: 25)

Exomes 𝑓: 0.000032 ( 8 hom. )

Consequence

OR4S2
NM_001004059.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.954

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.054076552).

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4S2	NM_001004059.3 linkuse as main transcript	c.232A>G	p.Lys78Glu	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.232A>G	p.Lys78Glu	missense_variant	2/2		NM_001004059.3	ENSP00000493389.1		Q8NH73

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

138292

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000855

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000713

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00216

GnomAD3 exomes

AF:

0.0000874

AC:

AN:

228752

Hom.:

AF XY:

0.0000807

AC XY:

AN XY:

123910

show subpopulations

Gnomad AFR exome

AF:

0.000624

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000638

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:

0.0000322

AC:

AN:

1335470

Hom.:

Cov.:

AF XY:

0.0000240

AC XY:

AN XY:

665600

show subpopulations

Gnomad4 AFR exome

AF:

0.000827

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000290

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000903

GnomAD4 genome

AF:

0.000304

AC:

AN:

138380

Hom.:

Cov.:

AF XY:

0.000312

AC XY:

AN XY:

67218

show subpopulations

Gnomad4 AFR

AF:

0.000877

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000715

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00216

Alfa

AF:

0.0000843

Hom.:

ESP6500AA

AF:

0.000687

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000953

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

Jul 14, 2021

The c.232A>G (p.K78E) alteration is located in exon 1 (coding exon 1) of the OR4S2 gene. This alteration results from a A to G substitution at nucleotide position 232, causing the lysine (K) at amino acid position 78 to be replaced by a glutamic acid (E). 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

0.41

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0072

T;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.3

M;M

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-3.3

.;D

REVEL

Benign

0.13

Sift

Uncertain

0.011

.;D

Sift4G

Uncertain

0.0030

.;D

Polyphen

0.94

P;P

Vest4

0.45

MVP

0.43

MPC

0.096

ClinPred

0.25

GERP RS

4.2

Varity_R

0.81

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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