Variant 11-48306282-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001004725.1(OR4S1):c.60G>T(p.Glu20Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000715 in 1,604,898 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 6 hom., cov: 28)

Exomes 𝑓: 0.00053 ( 21 hom. )

Consequence

OR4S1
NM_001004725.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.81

Variant links:

Genes affected

OR4S1 (HGNC:14705): (olfactory receptor family 4 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]

OR4S1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036590397).

BP6

Variant 11-48306282-G-T is Benign according to our data. Variant chr11-48306282-G-T is described in ClinVar as [Benign]. Clinvar id is 710008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4S1	NM_001004725.1 linkuse as main transcript	c.60G>T	p.Glu20Asp	missense_variant	1/1	ENST00000319988.1	NP_001004725.1	Q8NGB4A0A126GVU1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR4S1	ENST00000319988.1 linkuse as main transcript	c.60G>T	p.Glu20Asp	missense_variant	1/1	6	NM_001004725.1	ENSP00000321447.1		Q8NGB4

Frequencies

GnomAD3 genomes

AF:

0.00248

AC:

368

AN:

148452

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00779

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00645

Gnomad NFE

AF:

0.000344

Gnomad OTH

AF:

0.00301

GnomAD3 exomes

AF:

0.000877

AC:

220

AN:

250888

Hom.:

AF XY:

0.000745

AC XY:

101

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.00886

Gnomad AMR exome

AF:

0.000955

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000291

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.000534

AC:

777

AN:

1456332

Hom.:

Cov.:

AF XY:

0.000504

AC XY:

365

AN XY:

724506

show subpopulations

Gnomad4 AFR exome

AF:

0.00822

Gnomad4 AMR exome

AF:

0.00105

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000930

Gnomad4 FIN exome

AF:

0.0000750

Gnomad4 NFE exome

AF:

0.000324

Gnomad4 OTH exome

AF:

0.000963

GnomAD4 genome

AF:

0.00250

AC:

371

AN:

148566

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

172

AN XY:

72360

show subpopulations

Gnomad4 AFR

AF:

0.00784

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000345

Gnomad4 OTH

AF:

0.00297

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.00306

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00772

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00107

AC:

130

Asia WGS

AF:

0.000868

AC:

AN:

3472

EpiCase

AF:

0.000383

EpiControl

AF:

0.000416

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.5

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0087

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.17

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.3

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.4

REVEL

Benign

0.044

Sift

Benign

0.13

Sift4G

Benign

0.24

Polyphen

0.027

Vest4

0.11

MutPred

0.20

Loss of stability (P = 0.1886);

MVP

0.37

ClinPred

0.0043

GERP RS

0.40

Varity_R

0.086

gMVP

0.058

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