Genetic Variant OR2I1:p.Ala98Ala (chr6-29553512-C-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001396058.1(OR2I1):c.294C>G(p.Ala98Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 398,620 control chromosomes in the GnomAD database, including 5,838 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 ( 4405 hom., cov: 34)

Exomes 𝑓: 0.063 ( 1433 hom. )

Consequence

OR2I1
NM_001396058.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.60

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP7

Synonymous conserved (PhyloP=-4.6 with no splicing effect.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2I1	NM_001396058.1 link	c.294C>G	p.Ala98Ala	synonymous_variant	Exon 2 of 2	ENST00000641137.2	NP_001382987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2I1P	ENST00000641137.2 link	c.294C>G	p.Ala98Ala	synonymous_variant	Exon 2 of 2	NM_001396058.1	ENSP00000493715.1	A0A2R8Y4D9
OR2I1P	ENST00000641730.1 link	n.1156C>G		non_coding_transcript_exon_variant	Exon 2 of 2
OR2I1P	ENST00000642037.1 link	n.482C>G		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23939

AN:

152204

Hom.:

4373

Cov.:

show subpopulations

Gnomad AFR

AF:

0.441

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:

15433

AN:

246298

Hom.:

1433

Cov.:

AF XY:

0.0595

AC XY:

7429

AN XY:

124904

show subpopulations

African (AFR)

AF:

0.449

AC:

3217

AN:

7162

American (AMR)

AF:

0.0980

AC:

728

AN:

7426

Ashkenazi Jewish (ASJ)

AF:

0.0896

AC:

826

AN:

9222

East Asian (EAS)

AF:

0.185

AC:

4233

AN:

22892

South Asian (SAS)

AF:

0.150

AC:

454

AN:

3032

European-Finnish (FIN)

AF:

0.00892

AC:

186

AN:

20850

Middle Eastern (MID)

AF:

0.0978

AC:

127

AN:

1298

European-Non Finnish (NFE)

AF:

0.0265

AC:

4181

AN:

158058

Other (OTH)

AF:

0.0905

AC:

1481

AN:

16358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

1106

2212

3317

4423

5529

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:

24016

AN:

152322

Hom.:

4405

Cov.:

AF XY:

0.156

AC XY:

11614

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.442

AC:

18368

AN:

41546

American (AMR)

AF:

0.110

AC:

1677

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0916

AC:

318

AN:

3470

East Asian (EAS)

AF:

0.150

AC:

776

AN:

5180

South Asian (SAS)

AF:

0.145

AC:

703

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:

1702

AN:

68036

Other (OTH)

AF:

0.157

AC:

333

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

827

1653

2480

3306

4133

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:

0.102

Hom.:

361

Bravo

AF:

0.181

Asia WGS

AF:

0.136

AC:

474

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.5

(source)

DANN

Benign

0.69

PhyloP100

-4.6

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over