dbSNP rs16895070: OR2I1:p.Cys188Arg (chr6-29553780-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001396058.1(OR2I1):c.562T>C(p.Cys188Arg) variant causes a missense change. The variant allele was found at a frequency of 0.099 in 398,526 control chromosomes in the GnomAD database, including 5,850 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 4410 hom., cov: 33)

Exomes 𝑓: 0.063 ( 1440 hom. )

Consequence

OR2I1
NM_001396058.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.60

Publications

2 publications found

Variant links:

Genes affected

OR2I1 (HGNC:8258): (olfactory receptor family 2 subfamily I member 1 pseudogene) 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]

OR2I1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016171038).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001396058.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2I1	NM_001396058.1	MANE Select	c.562T>C	p.Cys188Arg	missense	Exon 2 of 2	NP_001382987.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OR2I1P	ENST00000641137.2	MANE Select	c.562T>C	p.Cys188Arg	missense	Exon 2 of 2	ENSP00000493715.1
OR2I1P	ENST00000641730.1		n.1424T>C		non_coding_transcript_exon	Exon 2 of 2
OR2I1P	ENST00000642037.1		n.750T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23952

AN:

152176

Hom.:

4378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.0916

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.00960

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0250

Gnomad OTH

AF:

0.160

GnomAD4 exome

AF:

0.0627

AC:

15440

AN:

246232

Hom.:

1440

Cov.:

AF XY:

0.0595

AC XY:

7423

AN XY:

124782

show subpopulations

African (AFR)

AF:

0.450

AC:

3229

AN:

7174

American (AMR)

AF:

0.0981

AC:

729

AN:

7432

Ashkenazi Jewish (ASJ)

AF:

0.0896

AC:

827

AN:

9234

East Asian (EAS)

AF:

0.185

AC:

4231

AN:

22888

South Asian (SAS)

AF:

0.149

AC:

453

AN:

3032

European-Finnish (FIN)

AF:

0.00893

AC:

186

AN:

20838

Middle Eastern (MID)

AF:

0.0981

AC:

127

AN:

1294

European-Non Finnish (NFE)

AF:

0.0264

AC:

4173

AN:

157976

Other (OTH)

AF:

0.0907

AC:

1485

AN:

16364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1129

2258

3386

4515

5644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.158

AC:

24029

AN:

152294

Hom.:

4410

Cov.:

AF XY:

0.156

AC XY:

11619

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.443

AC:

18378

AN:

41528

American (AMR)

AF:

0.110

AC:

1677

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0916

AC:

318

AN:

3472

East Asian (EAS)

AF:

0.150

AC:

780

AN:

5186

South Asian (SAS)

AF:

0.145

AC:

702

AN:

4832

European-Finnish (FIN)

AF:

0.00960

AC:

102

AN:

10630

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0250

AC:

1703

AN:

68016

Other (OTH)

AF:

0.157

AC:

332

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

812

1624

2437

3249

4061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

222

444

666

888

1110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.113

Hom.:

478

Bravo

AF:

0.181

TwinsUK

AF:

0.0183

AC:

ALSPAC

AF:

0.0189

AC:

Asia WGS

AF:

0.137

AC:

477

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Benign

0.89

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0016

PhyloP100

4.6

GERP RS

4.4

gMVP

0.23

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over