Variant 11-55651310-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001004059.3(OR4S2):c.407G>A(p.Arg136Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000309 in 1,488,102 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000029 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000031 ( 6 hom. )

Consequence

OR4S2
NM_001004059.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.80

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031994432).

BP6

Variant 11-55651310-G-A is Benign according to our data. Variant chr11-55651310-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3302967.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4S2	NM_001004059.3 linkuse as main transcript	c.407G>A	p.Arg136Gln	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.407G>A	p.Arg136Gln	missense_variant	2/2		NM_001004059.3	ENSP00000493389.1		Q8NH73

Frequencies

GnomAD3 genomes

AF:

0.0000290

AC:

AN:

137922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000252

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000788

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000240

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000161

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000962

AC:

AN:

228642

Hom.:

AF XY:

0.000137

AC XY:

AN XY:

123844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000830

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000761

Gnomad OTH exome

AF:

0.000178

GnomAD4 exome

AF:

0.0000311

AC:

AN:

1350180

Hom.:

Cov.:

AF XY:

0.0000372

AC XY:

AN XY:

671988

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000232

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000291

Gnomad4 OTH exome

AF:

0.0000537

GnomAD4 genome

AF:

0.0000290

AC:

AN:

137922

Hom.:

Cov.:

AF XY:

0.0000299

AC XY:

AN XY:

66802

show subpopulations

Gnomad4 AFR

AF:

0.0000252

Gnomad4 AMR

AF:

0.0000788

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000240

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000161

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000519

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.2

DANN

Benign

0.86

DEOGEN2

Benign

0.0080

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.0034

.;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.64

N;N

PrimateAI

Benign

0.17

PROVEAN

Uncertain

-2.5

.;D

REVEL

Benign

0.010

Sift

Benign

0.28

.;T

Sift4G

Benign

0.33

.;T

Polyphen

0.0090

B;B

Vest4

0.025

MutPred

0.47

Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);

MVP

0.14

MPC

0.039

ClinPred

0.016

GERP RS

-0.0011

Varity_R

0.064

gMVP

0.11

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