Genetic Variant OR1A2:p.Ala110Glu (chr17-3197847-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012352.3(OR1A2):c.329C>A(p.Ala110Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00489 in 1,611,618 control chromosomes in the GnomAD database, including 340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 165 hom., cov: 31)

Exomes 𝑓: 0.0028 ( 175 hom. )

Consequence

OR1A2
NM_012352.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.216

Publications

6 publications found

Variant links:

Genes affected

OR1A2 (HGNC:8180): (olfactory receptor family 1 subfamily A 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]

OR1A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036134124).

BP6

Variant 17-3197847-C-A is Benign according to our data. Variant chr17-3197847-C-A is described in ClinVar as Benign. ClinVar VariationId is 777088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012352.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1A2	NM_012352.3	MANE Select	c.329C>A	p.Ala110Glu	missense	Exon 1 of 1	NP_036484.1	A0A126GVH4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1A2	ENST00000381951.1	TSL:6 MANE Select	c.329C>A	p.Ala110Glu	missense	Exon 1 of 1	ENSP00000371377.1	Q9Y585

Frequencies

GnomAD3 genomes

AF:

0.0253

AC:

3849

AN:

152148

Hom.:

164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0872

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0121

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0149

GnomAD2 exomes

AF:

0.00688

AC:

1710

AN:

248368

AF XY:

0.00484

show subpopulations

Gnomad AFR exome

AF:

0.0915

Gnomad AMR exome

AF:

0.00498

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000223

Gnomad OTH exome

AF:

0.00363

GnomAD4 exome

AF:

0.00276

AC:

4026

AN:

1459352

Hom.:

175

Cov.:

AF XY:

0.00232

AC XY:

1687

AN XY:

725862

show subpopulations

African (AFR)

AF:

0.0926

AC:

3098

AN:

33464

American (AMR)

AF:

0.00562

AC:

251

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25908

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.000408

AC:

AN:

85844

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53140

Middle Eastern (MID)

AF:

0.00451

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000211

AC:

234

AN:

1110604

Other (OTH)

AF:

0.00632

AC:

381

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

212

424

635

847

1059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

208

312

416

520

<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:

0.0254

AC:

3861

AN:

152266

Hom.:

165

Cov.:

AF XY:

0.0244

AC XY:

1819

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0872

AC:

3621

AN:

41532

American (AMR)

AF:

0.0121

AC:

185

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68026

Other (OTH)

AF:

0.0166

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

181

362

544

725

906

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0203

Hom.:

Bravo

AF:

0.0297

ESP6500AA

AF:

0.0885

AC:

390

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00829

AC:

1006

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.025

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0036

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.5

PhyloP100

0.22

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.32

Sift

Uncertain

0.0040

Sift4G

Pathogenic

0.0010

Polyphen

0.28

Vest4

0.38

MVP

0.79

MPC

0.22

ClinPred

0.026

GERP RS

2.1

PromoterAI

0.024

Neutral

(source)

Varity_R

0.49

gMVP

0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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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