Genetic Variant OR6S1:p.Glu199Gly (chr14-20641096-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001001968.1(OR6S1):c.596A>G(p.Glu199Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00831 in 1,614,048 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 78 hom. )

Consequence

OR6S1
NM_001001968.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.933

Publications

13 publications found

Variant links:

Genes affected

OR6S1 (HGNC:15363): (olfactory receptor family 6 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]

OR6S1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050638914).

BP6

Variant 14-20641096-T-C is Benign according to our data. Variant chr14-20641096-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2644052.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR6S1	NM_001001968.1 link	c.596A>G	p.Glu199Gly	missense_variant	Exon 1 of 1	ENST00000320704.3	NP_001001968.1	Q8NH40

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR6S1	ENST00000320704.3 link	c.596A>G	p.Glu199Gly	missense_variant	Exon 1 of 1	6	NM_001001968.1	ENSP00000313110.3		Q8NH40

Frequencies

GnomAD3 genomes

AF:

0.00563

AC:

856

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00416

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00947

Gnomad OTH

AF:

0.00575

GnomAD2 exomes

AF:

0.00599

AC:

1507

AN:

251380

AF XY:

0.00612

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.00715

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.000971

Gnomad NFE exome

AF:

0.00953

Gnomad OTH exome

AF:

0.00620

GnomAD4 exome

AF:

0.00859

AC:

12557

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00841

AC XY:

6117

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

33480

American (AMR)

AF:

0.00273

AC:

122

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00593

AC:

155

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00525

AC:

453

AN:

86258

European-Finnish (FIN)

AF:

0.00120

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00971

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0100

AC:

11146

AN:

1111964

Other (OTH)

AF:

0.00851

AC:

514

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

699

1398

2097

2796

3495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00562

AC:

856

AN:

152206

Hom.:

Cov.:

AF XY:

0.00509

AC XY:

379

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00193

AC:

AN:

41536

American (AMR)

AF:

0.00425

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00416

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00947

AC:

644

AN:

68012

Other (OTH)

AF:

0.00569

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

140

187

234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00832

Hom.:

Bravo

AF:

0.00567

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.0119

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00942

AC:

ExAC

AF:

0.00633

AC:

769

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0107

EpiControl

AF:

0.00996

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

OR6S1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0071

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0051

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.4

PhyloP100

0.93

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-6.5

REVEL

Benign

0.15

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.21

MVP

0.77

MPC

0.084

ClinPred

0.035

GERP RS

5.6

Varity_R

0.93

gMVP

0.30

Mutation Taster

=94/6

polymorphism

(source)

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

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14-20641096-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over