dbSNP rs1567521265: OR1A2:p.Ile72Phe (chr17-3197732-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_012352.3(OR1A2):c.214A>T(p.Ile72Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,433,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

OR1A2
NM_012352.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.449

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05299896).

BP6

Variant 17-3197732-A-T is Benign according to our data. Variant chr17-3197732-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3204845.Status of the report is criteria_provided_single_submitter, 1 stars.

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.214A>T	p.Ile72Phe	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.214A>T	p.Ile72Phe	missense	Exon 1 of 1	ENSP00000371377.1	Q9Y585

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000209

AC:

AN:

1433492

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

709794

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33044

American (AMR)

AF:

0.00

AC:

AN:

42898

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23814

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39604

South Asian (SAS)

AF:

0.00

AC:

AN:

79796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51874

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5630

European-Non Finnish (NFE)

AF:

9.11e-7

AC:

AN:

1097564

Other (OTH)

AF:

0.00

AC:

AN:

59268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.0

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.0012

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.15

M_CAP

Benign

0.0061

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.28

PhyloP100

-0.45

PROVEAN

Benign

0.61

REVEL

Benign

0.21

Sift

Benign

0.23

Sift4G

Benign

0.17

Polyphen

0.0

Vest4

0.036

MutPred

0.54

Loss of stability (P = 0.1361)

MVP

0.37

MPC

0.23

ClinPred

0.066

GERP RS

0.43

PromoterAI

-0.017

Neutral

(source)

Varity_R

0.076

gMVP

0.12

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over